publications_chris.json

{
    "10.64898/2026.07.10.26357749": {
        "title": "Artificial intelligence-based ECG reconstruction error as a continuous predictor of all-cause mortality: a multi-cohort retrospective validation study",
        "journal": "medRxiv",
        "year": "2026",
        "abstract": "**Background**<br>Recent artificial intelligence (AI) models applied to the electrocardiogram (ECG) for risk stratification typically rely on supervised learning, defining risk as the error relative to an external target such as age or sex. This couples the risk score to the choice of target rather than the cardiac signal alone, and may limit generalisability. We aimed to develop a self-supervised AI-ECG risk score based on the error in reconstructing a partially masked ECG. <br>**Methods**<br>A transformer-based masked autoencoder was trained on 85% of the CODE dataset (n = 7,212,109 ECGs) to reconstruct ECG signals from partially masked inputs. The association between reconstruction error and all-cause mortality was assessed internally in CODE-15% and externally validated in four independent cohorts: MIMIC-IV-ECG (critical care, US), HEEDB (hospital, US), CHRIS (population-based, Italy), and Innsbruck (cardiology centre, Austria). A binary risk score (>1 SD above the CODE-15% mean) was additionally evaluated in these cohorts and in the UK Biobank (population-based, UK). <br>**Findings**<br>In Cox proportional hazards models adjusted for age and sex, each 1-SD increase in reconstruction error was associated with higher all-cause mortality (all *p* < 0.001; cohort median follow-up 1.4-11.0 years): CODE-15% (HR 1.39, 95% CI 1.37-1.42), MIMIC-IV-ECG (HR 1.39, 95% CI 1.37-1.40), HEEDB (HR 1.41, 95% CI 1.40-1.41), Innsbruck (HR 1.23, 95% CI 1.21-1.26), and CHRIS (HR 1.25, 95% CI 1.14-1.38). The binary threshold identified a high-risk group with increased mortality in all six cohorts, including the UK Biobank (HR 1.27, 95% CI 1.08-1.50, p=0.004).<br>**Interpretation**<br>Reconstruction error is a generalisable predictor of all-cause mortality across diverse clinical and population-based settings. Unlike supervised approaches, it reflects the model's uncertainty about the ECG signal itself rather than error relative to an external target, providing a direct measure of how much each recording deviates from normal cardiac electrical patterns.",
        "authors": [
            "Nicolson A",
            "Pr\u00f6ll S",
            "Lunelli R",
            "Blankenburg H",
            "Pramstaller P",
            "Fuchsberger C",
            "Bauer A",
            "Dlaska C"
        ],
        "doi": "10.64898/2026.07.10.26357749",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "570",
        "volume": "",
        "issue": "",
        "pages": "",
        "pre": true,
        "pdate": "2026-07-10"
    },
    "10.1007/s00394-026-03992-y": {
        "title": "Associations between dietary patterns and cardiovascular, kidney and metabolic risk markers in the Cooperative Health Research in South Tyrol study.",
        "journal": "European journal of nutrition",
        "year": "2026",
        "abstract": "**Purpose**<br> Cardiovascular-kidney metabolic syndrome (CKM) represents an increasingly prevalent public health concern. Optimal strategies to prevent CKM-related outcomes are greatly needed. We assessed the association between various dietary patterns and CKM biomarkers in a general population study. <br>**Methods**<br> We used cross-sectional data from 8066 adult participants of the Cooperative Health Research in South Tyrol (CHRIS) study. Self-reported dietary intake was assessed through the semi-quantitative GA<sup>2</sup>LEN Food Frequency questionnaire. We derived six established dietary pattern indices, and population-specific dietary patterns through principal component analysis. CKM biomarkers included: systolic and diastolic blood pressure, glycated haemoglobin, visceral fat, HDL, LDL and total cholesterol, triglycerides, creatinine-based estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio. We investigated associations between each dietary index and CKM risk marker using multivariable linear regression models. We further examined potential effect modification by sex, body mass index, physical activity and smoking habit. <br>**Results**<br> Higher adherence to healthy dietary patterns rich in fruits, vegetables, whole grains, and low in saturated fats was associated with more favorable CKM marker levels. E.g, when comparing the fourth to the first quartile the healthy plant-based dietary index was associated with lower total and LDL cholesterol (\u03b2\u00a0\u2248\u00a0-\u00a0\u20095.0\u00a0mg/dL, *p*\u00a0<\u00a0\u20090.001), lower blood pressure (\u03b2=\u00a0-\u00a01.24 mmHg, *p*\u2009=\u20090.001) and higher eGFR (\u03b2\u2009=\u20091.24\u00a0ml/min/1.73m<sup>2</sup>, *p*\u2009=\u20090.001). In contrast, the unhealthy plant based and a Western style diet were associated with higher SBP (\u03b2\u00a0\u2009=\u00a0\u20091.23-1.89\u00a0mmHg, *p*\u00a0<\u00a00.01), amongst others. For some markers, associations tended to be stronger in men, individuals with overweight or obesity, those with lower physical activity, and smokers (*P<sub>interaction</sub>*<\u00a00.05). <br>**Conclusions**<br> Adhering to a healthy plant rich diet low in saturated fats, added sugars and processed foods was associated with more favorable levels of CKM biomarkers, including blood lipids, blood pressure, glycated hemoglobin and eGFR.",
        "authors": [
            "Hantikainen E",
            "Berger S",
            "Barbieri G",
            "Pramstaller PP",
            "Garcia-Larsen V",
            "G\u00f6gele M",
            "Pattaro C",
            "Lundin R",
            "Domingues FS"
        ],
        "doi": "10.1007/s00394-026-03992-y",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "537",
        "volume": "65",
        "issue": "4",
        "pages": "",
        "pre": false,
        "pdate": "2026-05-29"
    },
    "10.64898/2025.12.01.25341334": {
        "title": "Molecular characterization of liver steatosis through circulating proteins, metabolites and lipids",
        "journal": "medRxiv",
        "year": "2025",
        "abstract": "**Background**<br> Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most prevalent liver disorders in Western countries. While steatosis is prevalent, molecular mechanisms associated with steatosis grades and how nutrition modulates related metabolic disturbances remain poorly understood. <br>**Methods**<br> We analyzed data from 327 participants of the CHRIS NAFLD study with Type 2 diabetes (T2D) and matched controls, integrating 148 plasma proteins with 175 serum metabolites and lipids to identify circulating biomarkers associated with hepatic steatosis severity. Associations between dietary intake and steatosis were investigated, and a potential influence of diet on the identified biomarkers was evaluated through a sensitivity analysis. Participants were stratified by steatosis grade based on ultrasound-derived measurements. <br>**Results**<br> Steatosis grade was strongly positively correlated with BMI and T2D. Several proteins (e.g., GC, AFM, AZGP1, SERPINC1, VTN, LRG1) and metabolites (e.g., glutamate, tyrosine, valine, lysoPCs) were associated with the highest steatosis grade, mainly reflecting a broader metabolically unhealthy phenotype. Adherence to a plant-based diet was associated with lower steatosis grades independent of circulating proteins, metabolites, and lipids. <br>**Conclusion**<br> Results suggest that circulating metabolic signatures of steatosis reflect broader metabolic dysregulation and are independent of dietary intake. These data support the use of blood-based multi-omics profiling to distinguish between metabolically healthy and unhealthy individuals, and may thus improve MASLD risk stratification.",
        "authors": [
            "De Graeve M",
            "Hantikainen E",
            "Louail P",
            "Verri Hernandes V",
            "Pattaro C",
            "Domingues FS",
            "Pramstaller PP",
            "Tilg H",
            "Ralser M",
            "Grander C",
            "Rainer J"
        ],
        "doi": "10.64898/2025.12.01.25341334",
        "source_study": [
            "CHRIS NAFLD"
        ],
        "ar": "534",
        "volume": "",
        "issue": "",
        "pages": "",
        "pre": true,
        "pdate": "2025-12-01"
    },
    "10.1016/j.celrep.2023.113611": {
        "title": "Genetic determinants of complement activation in the general population.",
        "journal": "Cell reports",
        "year": "2024",
        "abstract": "Complement is a fundamental innate immune response component. Its alterations are associated with severe systemic diseases. To illuminate the complement's genetic underpinnings, we conduct genome-wide association studies of the functional activity of the classical (CP), lectin (LP), and alternative (AP) complement pathways in the Cooperative Health Research in South Tyrol study (n\u00a0= 4,990). We identify seven loci, encompassing 13 independent, pathway-specific variants located in or near complement genes (*CFHR4*, *C7*, *C2*, *MBL2*) and non-complement genes (*PDE3A*, *TNXB*, *ABO*), explaining up to 74% of complement pathways' genetic heritability and implicating long-range haplotypes associated with LP at *MBL2*. Two-sample Mendelian randomization analyses, supported by transcriptome- and proteome-wide colocalization, confirm known causal pathways, establish within-complement feedback loops, and implicate causality of ABO on LP and of CFHR2 and C7 on AP. LP causally influences collectin-11 and KAAG1 levels and the risk of mouth ulcers. These results build a comprehensive resource to investigate the role of complement in human health.",
        "authors": [
            "Noce D",
            "Foco L",
            "Orth-H\u00f6ller D",
            "K\u00f6nig E",
            "Barbieri G",
            "Pietzner M",
            "Ghasemi-Semeskandeh D",
            "Coassin S",
            "Fuchsberger C",
            "G\u00f6gele M",
            "Del Greco M F",
            "De Grandi A",
            "Summerer M",
            "Wheeler E",
            "Langenberg C",
            "Lass-Fl\u00f6rl C",
            "Pramstaller PP",
            "Kronenberg F",
            "W\u00fcrzner R",
            "Pattaro C"
        ],
        "doi": "10.1016/j.celrep.2023.113611",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "346",
        "volume": "43",
        "issue": "1",
        "pages": "113611",
        "pre": false,
        "pdate": "2024-01-02"
    },
    "10.1038/s41467-025-61330-y": {
        "title": "Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants.",
        "journal": "Nature communications",
        "year": "2025",
        "abstract": "Smelling is a human sense, expressing strong sexual dimorphisms. We aim to improve the knowledge of the genetics of human olfactory perception by performing an exploratory genome-wide association meta-analysis of up to 21,495 individuals of European ancestry. By sex-stratified and overall analysis of the identification of twelve odours and an identification score, we discovered ten independent loci, seven of them novel, with trait-wise genome-wide significance (*p*\u2009<\u20095 \u00d7 10<sup>-8</sup>) involving five odours. Seven of these loci, including four novel ones, are also significant using a stricter study-wide significance threshold (*p*\u2009<\u20093.85 \u00d7 10<sup>-9</sup>). Loci were predominantly located within clusters of olfactory receptors. Two loci were female-specific while one was sex-differential with respective candidate genes containing androgen response elements. Two-sample Mendelian randomization was applied to search for causal relationships between sex hormones, odour identification and neurodegenerative diseases. A causal negative effect was detected for Alzheimer's disease on the identification score. These findings deepen our understanding of the genetic basis of olfactory perception and its interaction with sex, prioritizing mechanisms for further molecular research.",
        "authors": [
            "F\u00f6rster F",
            "Emmert D",
            "Horn K",
            "Pott J",
            "Frasnelli J",
            "Imtiaz MA",
            "Melas K",
            "Talevi V",
            "Chen H",
            "Engel C",
            "Filosi M",
            "Fornage M",
            "G\u00f6gele M",
            "L\u00f6ffler M",
            "Mosley TH",
            "Pattaro C",
            "Pramstaller P",
            "Shrestha S",
            "Aziz NA",
            "Breteler MMB",
            "Wirkner K",
            "Scholz M",
            "Fuchsberger C"
        ],
        "doi": "10.1038/s41467-025-61330-y",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "511",
        "volume": "16",
        "issue": "1",
        "pages": "5434",
        "pre": false,
        "pdate": "2025-07-02"
    },
    "10.1093/ckj/sfag196": {
        "title": "Combined effects of diet and genetic predisposition on kidney function outcomes",
        "journal": "Clinical Kidney Journal",
        "year": "2026",
        "abstract": "Chronic kidney disease (CKD) is a significant global health concern. While diet is crucial to CKD prevention and management, the interaction between diet and genetic predisposition to CKD is underexplored. We conducted an exploratory investigation of the interplay between a polygenic score (PGS) for kidney function and dietary exposures in relation to glomerular filtration rate estimated based on serum creatinine (eGFRcrea) on 5717 generally healthy adult participants of the Cooperative Health Research In South Tyrol (CHRIS) study.Dietary intake was assessed using the GA2LEN food frequency questionnaire, from which we derived dietary quality indices including the Mediterranean, Alternative Healthy Eating Index (AHEI) and Dietary Approaches to Stop Hypertension (DASH) diets, and nutrients relevant to kidney function (proteins, potassium and phosphorus). Genetic predisposition to lower kidney function was quantified using a PGS derived from 131 single nucleotide polymorphisms (SNPs) whose risk alleles were associated with lower eGFRcrea and higher blood urea nitrogen. We fitted multivariable generalized additive models incorporating diet-by-PGS interaction terms to model non-linear associations with eGFRcrea.The PGS was linearly associated with eGFRcrea (estimated degrees of freedom, df = 1.00, *P* < 0.0001), regardless of dietary exposures. All nutrients showed significant linear negative associations with eGFRcrea, a pattern not observed for dietary indices. Nominally significant non-linear interactions were observed between the PGS and both protein (df = 4.93, *P* = 0.0298) and phosphorus intake (df = 5.37, *P* = 0.0283).The association of dietary protein and phosphorus intake with eGFRcrea may vary by genetic predisposition to low eGFRcrea levels, with stronger dietary effects in those with a high genetic predisposition.",
        "authors": [
            "Barbieri G",
            "Fujii R",
            "Filosi M",
            "Ghasemi-Semeskandeh D",
            "G\u00f6gele M",
            "Malerba G",
            "Zanolin ME",
            "Cazzoletti L",
            "Pramstaller PP",
            "Pattaro C",
            "Hantikainen E"
        ],
        "doi": "10.1093/ckj/sfag196",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "509",
        "volume": "",
        "issue": "",
        "pages": "sfag196",
        "pre": false,
        "pdate": "2026-01-01"
    },
    "10.1007/s00439-025-02761-x": {
        "title": "Genomic and molecular evidence that the LncRNA DSP-AS1 modulates desmoplakin expression.",
        "journal": "Human genetics",
        "year": "2025",
        "abstract": "Cardiac desmosomes are specialized cell junctions responsible for cardiomyocytes mechanical coupling. Mutation in desmosomal genes cause autosomal dominant and recessive familial arrhythmogenic cardiomyopathy. Motivated by evidence that Mendelian diseases share genetic architecture with common complex traits, we assessed whether common variants in any desmosomal gene were associated with cardiac conduction traits in the general population. We analysed data of N\u2009=\u20094342 Cooperative Health Research in South Tyrol (CHRIS) study participants. We tested associations between genotype imputed variants covering the five desmosomal genes Desmoplakin (*DSP*), junction plakoglobin *(JUP)*, plakophilin 2 *(PKP2)*, desmoglein 2 *(DSG2)*, and desmocollin 2 *(DSC2)*, and P-wave, PR, QRS, and QT electrocardiographic intervals, using linear mixed models. Functional annotation and interrogation of publicly available genome-wide association study resources implicated potential connection with antisense long non-coding RNAs (lncRNAs), DNA methylation sites, and complex traits. Causality was tested via two-sample Mendelian randomization (MR) analysis and validated with functional in vitro follow-up in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). *DSP* variant rs2744389 was associated with QRS (*P*\u2009=\u20093.5\u2009\u00d7\u200910<sup>-6</sup>), with replication in the Microisolates in South Tyrol (MICROS) study (n\u2009=\u2009636; *P*\u2009=\u20090.010). Observing that rs2744389 was associated with *DSP-AS1* antisense lncRNA but not with *DSP* expression in multiple Genotype-Tissue Expression (GTEx) v8 tissues, we conducted two-sample Mendelian randomization analyses that identified causal effects of *DSP-AS1* on *DSP* expression (*P*\u2009=\u20096.33\u2009\u00d7\u200910<sup>-5</sup>); colocalization posterior probability\u2009=\u20090.91) and QRS (*P*\u2009=\u20090.015). In hiPSC-CMs, *DSP-AS1* expression downregulation through a specific GapmerR matching sequence led to significant *DSP* upregulation at both mRNA and protein levels. The evidence that *DSP-AS1* has a regulatory role on *DSP* opens the venue for further investigations on *DSP-AS1'*s therapeutic potential for conditions caused by reduced desmoplakin production.",
        "authors": [
            "Foco L",
            "De Bortoli M",
            "Del Greco M F",
            "Frommelt LS",
            "Volani C",
            "Riekschnitz DA",
            "Motta BM",
            "Fuchsberger C",
            "Delerue T",
            "V\u00f6lker U",
            "Huan T",
            "G\u00f6gele M",
            "Winkelmann J",
            "D\u00f6rr M",
            "Levy D",
            "Waldenberger M",
            "Teumer A",
            "Pramstaller PP",
            "Rossini A",
            "Pattaro C"
        ],
        "doi": "10.1007/s00439-025-02761-x",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "454",
        "volume": "144",
        "issue": "8",
        "pages": "843-860",
        "pre": false,
        "pdate": "2025-07-30"
    },
    "10.1101/2025.06.12.25329492": {
        "title": "Haplomics: A Snakemake pipeline for haplotype-based association analysis in multi-omics studies",
        "journal": "medRxiv",
        "year": "2025",
        "abstract": "Genome-wide association studies (GWAS) generated thousands of loci associated with complex traits and diseases. However, to characterize of the pleiotropic, molecular and population genetic bounds of uncovered loci, investigations are conducted, that remain conceptually and practically separated. Also in the best case, such investigations proceed by one locus at a time. To address these limitations, we introduce an efficient and reproducible Snakemake pipeline for executing haplotype-based association analysis on GWAS-identified genetic loci, which is especially helpful in samples enriched with molecular omics data. Haplomics takes as input the genetic coordinates of each locus along with all available clinical and molecular phenotypes, the necessary covariates, and VCF genotype files, to reconstruct haplotypes and test them for associations with the phenotypes. The reconstructed haplotypes, the annotation of included variants, and association results are graphically displayed in an HTML report. We tested Haplomics in population-based study sample encompassing 391 traits, including 72 clinical markers, 171 serum metabolites, 148 plasma protein concentrations, and whole-exome sequencing (WES) imputed genotypes. We estimated WES-based haplotypes at 11 kidney function genetic loci from a GWAS and conducted association analyses throughout, identifying 19 significant associations after multiple testing correction. Haplomics is a scalable, easy-to-use and fast haplotype reconstruction and association pipeline that makes it possible to jointly conduct molecular and population-genetic characterization of multiple GWAS loci in unified analysis framework.",
        "authors": [
            "Ghasemi-Semeskandeh D",
            "Foco L",
            "Fujii R",
            "Rainer J",
            "Feli M",
            "Ralser M",
            "Domingues FS",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1101/2025.06.12.25329492",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "502",
        "volume": "",
        "issue": "",
        "pages": "",
        "pre": true,
        "pdate": "2025-06-12"
    },
    "10.1093/gigascience/giaf140": {
        "title": "NApy: Efficient Statistics in Python for Large-Scale Heterogeneous Data with Enhanced Support for Missing Data.",
        "journal": "GigaScience",
        "year": "2025",
        "abstract": "Existing Python libraries and tools lack the ability to efficiently compute statistical test results for large datasets in the presence of missing values. This presents an issue as soon as constraints on runtime and memory availability become essential considerations for a particular use case. Relevant research areas where such limitations arise include interactive tools and databases for exploratory analysis of biomedical data. To address this problem, we present the Python package NApy, which relies on a Numba and C++ backend with OpenMP parallelization to enable scalable statistical testing for mixed-type datasets in the presence of missing values. Both with respect to runtime and memory consumption, NApy outperforms competitor tools and baseline implementations with na\u00efve Python-based parallelization by orders of magnitude, thereby enabling on-the-fly analyses in interactive applications. NApy is publicly available at [https://github.com/DyHealthNet/NApy](https://github.com/DyHealthNet/NApy).",
        "authors": [
            "Woller F",
            "Arend L",
            "Fuchsberger C",
            "List M",
            "Blumenthal DB"
        ],
        "doi": "10.1093/gigascience/giaf140",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "492",
        "volume": "",
        "issue": "",
        "pages": "",
        "pre": false,
        "pdate": "2025-11-09"
    },
    "10.1101/2025.03.10.25323679": {
        "title": "Characterization of metabolically healthy and unhealthy obesity through circulating proteins and metabolites",
        "journal": "medRxiv",
        "year": "2025",
        "abstract": "**Background** <br> Individuals affected by obesity present different health trajectories and do not suffer from cardiometabolic complications all in the same way. There is a need to better understand obesity subtypes and to develop approaches for stratification. In this study we investigated both metabolomic and proteomic signatures in serum and blood plasma samples discriminating metabolically healthy from unhealthy obesity.<br>**Methods**<br> We investigated cross-sectional metabolomic and proteomic data from participants of the Cooperative Health Research in South Tyrol (CHRIS) study. Participants were grouped into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) based on available health data in the study. A total of 461 individuals were included in the analysis, with n=130 MHO and n=331 MUO. Random forest (RF) classifiers were used to discriminate metabolically healthy from unhealthy obesity and to identify molecular features characteristic of MHO/MUO. Linear regression models were used to assess associations between each relevant metabolite/protein and MHO/MUO phenotypes independently of age, sex and body composition.<br>**Results**<br> The MHO/MUO RF classifier achieved a performance of AUC = 0.709, 95% CI = (0.698,0.721). Three plasma proteins and 12 circulating metabolites were identified as relevant predictors of MHO/MUO phenotypes. Linear regression models confirmed the Apolipoprotein C-III (APOC3) association to be independent of age, visceral fat composition, medication or serum triglyceride levels.<br>**Conclusion**<br> APOC3 was identified as a novel predictor for obesity stratification, highlighting the importance of circulating triglyceride levels in relation to metabolic health.",
        "authors": [
            "Pontali G",
            "Weichenberger CX",
            "Rainer J",
            "Hantikainen E",
            "De Graeve M",
            "Mattivi F",
            "Kob M",
            "Ralser M",
            "Pramstaller PP",
            "Domingues FS"
        ],
        "doi": "10.1101/2025.03.10.25323679",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "489",
        "volume": "",
        "issue": "",
        "pages": "",
        "pre": true,
        "pdate": "2025-03-10"
    },
    "10.1159/000546975": {
        "title": "Impact of Living in a Mountain Environment on Health and Mortality: Insights from the Alpine Population in Northern Italy.",
        "journal": "Gerontology",
        "year": "2025",
        "abstract": "**Introduction**<br> Residing at moderate altitudes has been associated with various health benefits also affecting mortality risk. This study investigates life expectancy and disease-specific mortality rates among populations in the Italian Alps and in northern Italian lowland regions. Additionally, cardiometabolic health and serum metabolite concentrations of residents in an Alpine province across three distinct elevation zones (<1,000 m, 1,000-1,500 m, and >1,500 m above sea level) are studied. <br>**Methods**<br> Data on life expectancy and mortality rate (per ten thousand) were retrieved from the ISTAT database for 6 provinces located in the Italian Alps and 6 provinces at sea level near the Alps. Using cross-sectional data from a sub-sample of the Cooperative Health Research in South Tyrol (CHRIS) study (n=6,292), we fitted multivariable adjusted logistic regression models to investigate associations between altitude and cardiometabolic health, determined by the Cumulative Illness Rating Scale. Moreover, associations between altitude and 175 serum metabolites were evaluated through linear regression models (n=1,447). <br>**Results**<br> Population size and sex distribution were similar between provinces (p>0.485). Life expectancy at 65 years differed between areas (20.8\u00b10.4 vs 20.1\u00b10.3, for Alps vs sea-level, respectively, p=0.026). Mortality rate for diseases of the circulatory system was lower in the Alps than at sea-level (35.3\u00b15.7 vs. 44.5\u00b16.8, respectively, p=0.026). No statistically significant differences were found for mortality (Alps vs. sea-level) from all causes (108.1\u00b115.7 vs. 126.1\u00b115.5, *p*=0.065), cerebrovascular diseases (8.4\u00b12.5 vs. 12.6\u00b13.1, *p*=0.065), endocrine, nutritional and metabolic diseases (3.6\u00b11.0 vs. 5.0\u00b11.0, *p*=0.065), neoplasms (31.1\u00b14.7 vs. 34.3\u00b12.4 *p*=0.394) and diseases of the respiratory system (8.3\u00b11.7 vs. 8.8\u00b11.7, *p*=0.589). In the CHRIS study sample, living at moderate vs. low altitude level was associated with lower odds of mild to severe conditions in the hypertension (OR:0.77; 95%CI: 0.62-0.96) and endocrine-metabolic domain (OR:0.77, 95%CI: 0.61-0.97). No differences in blood serum metabolic profiles were observed between people living at different altitude levels. <br>**Conclusions**<br> Living in the Italian Alps seems to have a positive effect on life expectancy and mortality from certain diseases compared to living at sea level in northern Italy. Furthermore, living at moderate altitude conferred some cardiometabolic health benefits in the CHRIS study population, even after corrections for confounding factors. The metabolite profile in a sub-sample did, however, not reveal any significant differences between altitude levels.",
        "authors": [
            "Hantikainen E",
            "Dordevic N",
            "Neunhaeuserer D",
            "Pramstaller PP",
            "Rainer J",
            "Gatterer H"
        ],
        "doi": "10.1159/000546975",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "484",
        "volume": "",
        "issue": "",
        "pages": "1-22",
        "pre": false,
        "pdate": "2025-06-17"
    },
    "10.1007/s00439-017-1785-8": {
        "title": "Sequential recruitment of study participants may inflate genetic heritability estimates.",
        "journal": "Human genetics",
        "year": "2017",
        "abstract": "After the success of genome-wide association studies to uncover complex trait loci, attempts to explain the remaining genetic heritability (h <sup>2</sup>) are mainly focused on unraveling rare variant associations and gene-gene or gene-environment interactions. Little attention is paid to the possibility that h <sup>2</sup> estimates are inflated as a consequence of the epidemiological study design. We studied the time series of 54 biochemical traits in 4373 individuals from the Cooperative Health Research In South Tyrol (CHRIS) study, a pedigree-based study enrolling ten participants/day over several years, with close relatives preferentially invited within the same day. We observed distributional changes of measured traits over time. We hypothesized that the combination of such changes with the pedigree structure might generate a shared-environment component with consequent h <sup>2</sup> inflation. We performed variance components (VC) h <sup>2</sup> estimation for all traits after accounting for the enrollment period in a linear mixed model (two-stage approach). Accounting for the enrollment period caused a median h <sup>2</sup> reduction of 4%. For 9 traits, the reduction was of >20%. Results were confirmed by a Bayesian Markov chain Monte Carlo analysis with all VCs included at the same time (one-stage approach). The electrolytes were the traits most affected by the enrollment period. The h <sup>2</sup> inflation was independent of the h <sup>2</sup> magnitude, laboratory protocol changes, and length of the enrollment period. The enrollment process may induce shared-environment effects even under very stringent and standardized operating procedures, causing h <sup>2</sup> inflation. Including the day of participation as a random effect is a sensitive way to avoid overestimation.",
        "authors": [
            "Noce D",
            "G\u00f6gele M",
            "Schwienbacher C",
            "Caprioli G",
            "De Grandi A",
            "Foco L",
            "Platzgummer S",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1007/s00439-017-1785-8",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "477",
        "volume": "136",
        "issue": "6",
        "pages": "743-757",
        "pre": false,
        "pdate": "2017-04-05"
    },
    "10.1053/j.jrn.2024.03.003": {
        "title": "Associations Between Dietary Patterns and Kidney Health Assessed in the Population-Based CHRIS Study Using Reduced Rank Regression.",
        "journal": "Journal of renal nutrition",
        "year": "2024",
        "abstract": "**Objective**<br> While diet plays a key role in chronic kidney disease (CKD) management, the potential for diet to impact CKD prevention in the general population is less clear. Using a priori knowledge, we derived disease-related dietary patterns (DPs) through reduced rank regression (RRR) and investigated associations with kidney function, separately focusing on generally healthy individuals and those with self-reported kidney diseases, hypertension, or diabetes mellitus. <br>**Methods**<br> Eight thousand six hundred eighty-six participants from the population-based Cooperative Health Research in South Tyrol study were split into a group free of kidney disease, hypertension and diabetes (n\u00a0=\u00a06,133) and a group with any of the 3 conditions (n\u00a0=\u00a02,553). Diet was assessed through the self-administered Global Allergy and Asthma Network of Excellence food frequency questionnaire and DPs were derived through RRR selecting food frequency questionnaire-derived sodium, potassium, phosphorus, and protein intake as mediators. Outcomes were creatinine-based estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, CKD and microalbuminuria. Multiple linear and logistic models were used to assess associations between RRR-based DPs and kidney outcomes separately in the 2 analytic groups. <br>**Results**<br> We identified 3 DPs, where high adherence reflected high levels of all nutrients (DP1), high potassium-phosphorus and low protein-sodium levels (DP2), and low potassium-sodium and high protein-phosphorus levels (DP3), respectively. We observed heterogeneous associations with kidney outcomes, varying by analytic group and sex. Kidney outcomes were much more strongly associated with DPs than with single nutrients. <br>**Conclusion**<br> RRR is a feasible approach to estimate disease-related DPs and explore the combined effects of nutrients on kidney health. Heterogeneous associations across kidney outcomes suggest possible specificity to kidney function or damage. In individuals reporting kidney disease, hypertension or diabetes, specific dietary habits were associated with better kidney health, indicating that disease-specific dietary interventions can be effective for disease control.",
        "authors": [
            "Barbieri G",
            "Garcia-Larsen V",
            "Lundin R",
            "Fujii R",
            "Melotti R",
            "G\u00f6gele M",
            "Christopher KB",
            "Cazzoletti L",
            "Pramstaller PP",
            "Zanolin ME",
            "Pattaro C",
            "Hantikainen E"
        ],
        "doi": "10.1053/j.jrn.2024.03.003",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "398",
        "volume": "34",
        "issue": "5",
        "pages": "427-437",
        "pre": false,
        "pdate": "2024-03-24"
    },
    "10.1186/s12882-026-04896-z": {
        "title": "DASH diet, Reduced Rank Regression Dietary Patterns and relations with kidney function in the CHRIS general population study.",
        "journal": "BMC nephrology",
        "year": "2026",
        "abstract": "**Background**<br> Chronic kidney disease (CKD) is a growing public health concern, closely linked to aging and chronic conditions such as diabetes, cardiovascular disease, and hypertension. Diet is a modifiable risk factor for kidney function, but evidence on how specific dietary patterns (DPs) relate to kidney health in healthy populations remains limited. To address this, we evaluated associations between DPs and kidney function, considering sex and menstrual status. DPs were derived using both an a priori approach (DASH) and a hybrid method (RRR), capturing established dietary recommendations as well as population-specific behaviours relevant to kidney health. <br>**Methods**<br> We analysed cross-sectional data from 6133 healthy adult participants of the Cooperative Health Research In South Tyrol (CHRIS) study. Participants self-reporting previous diagnoses of any kidney disease, hypertension, or diabetes were excluded. Using self-reported food frequency questionnaire data, we derived the DASH-score and two RRR-based sex-specific DP-scores based on nine cardio-renal-metabolic parameters. We applied sex-stratified linear and non-linear models to examine associations with creatinine-based eGFR, including interaction and stratified analyses by menstrual status in females. <br>**Results**<br> In males, a DP reflecting high intake of cereals, whole grains, sugar, fruits, and legumes, and low intake of beer, red and processed meat was associated with higher eGFR levels (\u03b2\u2009=\u20090.75, *p*\u2009=\u20090.0001). Similarly, higher adherence to the DASH diet was also positively associated with eGFR (\u03b2\u2009=\u20090.64, *p*\u2009=\u20090.0029). In females, the associations varied by menstrual status. Among those with ceased menstruation, a DP reflecting low intake of meat, spirits, and refined grains, and high intake of whole grains and dairy products was associated with higher eGFR (\u03b2\u2009=\u20091.11, *p*\u2009=\u20090.0049). In females still experiencing regular menstruation, a DP reflecting high intake of beef, nuts, beer, and legumes, and low intake of refined grains was associated with lower eGFR (\u03b2\u2009=\u2009\u22120.43, *p*\u2009=\u20090.0326). No association was observed with the DASH score in females.<br>**Conclusions**<br>  The DASH-style diet is associated with better kidney function in males, but not in females. Identifying sex-specific kidney function-oriented DPs using RRR provides new insights into the diet-eGFR relationship, suggesting potential effect modification by menstrual status.",
        "authors": [
            "Barbieri G",
            "Garcia-Larsen V",
            "Lundin R",
            "Fujii R",
            "Ferraro PM",
            "Gambaro G",
            "Melotti R",
            "G\u00f6gele M",
            "Cazzoletti L",
            "Pramstaller PP",
            "Zanolin ME",
            "Pattaro C",
            "Hantikainen E"
        ],
        "doi": "10.1186/s12882-026-04896-z",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "459",
        "volume": "27",
        "issue": "1",
        "pages": "",
        "pre": false,
        "pdate": "2026-04-21"
    },
    "10.1007/s40620-024-02157-6": {
        "title": "Development and evaluation of a kidney health questionnaire and estimates of chronic kidney disease prevalence in the Cooperative Health Research in South Tyrol (CHRIS) study.",
        "journal": "Journal of nephrology",
        "year": "2025",
        "abstract": "**Background**<br> Kidney diseases are a public health burden but are poorly investigated in the general population. In light of inadequate survey tools, we developed a novel questionnaire for use in population-based studies, to retrospectively assess kidney diseases. <br>**Methods**<br> The questionnaire covered general kidney diseases, reduced kidney function, and renal surgeries. It was administered between 2011 and 2018 to 11,684 participants (median age\u2009=\u200945 years) of the Cooperative Health Research in South Tyrol (CHRIS) study. Fasting estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were measured. By factor analysis we contextualized the questionnaire content with respect to the\u00a0biochemical measurements. We estimated overall and sex-stratified prevalence of kidney diseases, including possible CKD, calibrating them to the general target population via relative sampling weights. <br>**Results**<br> Population-representative prevalence of glomerulonephritis, pyelonephritis, and congenital kidney diseases was 1.0%, 3.0%, and 0.2%, respectively, with corresponding odds ratios for females versus males of 1.4 (95% confidence interval: 1.0, 2.0), 8.7 (6.2, 12.3), and 0.7 (0.3, 1.6), respectively. Prevalence of kidney dysfunction (eGFR\u2009<\u200960\u00a0mL/min/1.73\u00a0m(2) or UACR\u2009>\u200930\u00a0mg/g) was 8.59%, while prevalence of self-reported CKD was 0.69%, indicating 95.3% of\u00a0lack of disease awareness, with a similar figure in people with diabetes or hypertension. Overall, 15.76% of the population was affected by a kidney disease of any kind. <br>**Conclusion**<br> In the Val Venosta/Vinschgau alpine district, CKD prevalence aligned with Western European estimates. Kidney health questionnaire implementation in population studies is feasible and valuable to assess CKD awareness, which we found to be dramatically low.",
        "authors": [
            "Barbieri G",
            "Cazzoletti L",
            "Melotti R",
            "Hantikainen E",
            "Lundin R",
            "Barin L",
            "G\u00f6gele M",
            "Riegler P",
            "Ferraro PM",
            "Pramstaller PP",
            "Gambaro G",
            "Zanolin ME",
            "Pattaro C"
        ],
        "doi": "10.1007/s40620-024-02157-6",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "442",
        "volume": "38",
        "issue": "2",
        "pages": "521-530",
        "pre": false,
        "pdate": "2024-11-27"
    },
    "10.1016/j.jad.2025.03.055": {
        "title": "The influence of affective temperaments on sleep quality in a general population sample. Data report from the CHRIS study.",
        "journal": "Journal of affective disorders",
        "year": "2025",
        "abstract": "**Background**<br> Affective temperaments predispose to life adaptation and affective disorders. The relationship between temperaments and sleep quality is rarely investigated in community-based studies. We hypothesized that cyclothymic-related temperaments relate to worse sleep quality, whereas the hyperthymic temperament favours sleep quality. <br>**Method**<br> We investigated 3701 18 to 65\u00a0years old adults from the population-based CHRIS study in Italy. Participants were 54\u00a0% females, mean age 38.5\u00a0years. The Pittsburgh Sleep Quality Index (PSQI) was the primary outcome score. Five affective temperaments split into quartiles for direct comparison from the TEMPS-M questionnaire were the exposures of interest. Additional covariates comprised sex, age, trait anxiety, and sleep quality-related lifestyles assessed via interviews, self-administered questionnaires or instrumental measurements. <br>**Results**<br> The hyperthymic temperament showed a negative association (better sleep quality) with the global PSQI, whereas the cyclothymic-related temperaments had all associations in opposite direction. While inclusion of trait anxiety appeared to mediate some results, the anxious and other cyclothymic related temperaments were still directly associated with multiple dimensions of poor sleep quality. <br>**Limitations**<br> The cross-sectional design, possible selection into the study by temperamental background or sleep disorders, and no clinically validated self-assessed psychiatric constructs represent possible weaknesses. <br>**Conclusions**<br> Our findings support the hypothesis of a biological binary diathesis of affective temperaments, with hyperthymic and cyclothymic-related temperaments predisposing sleep quality in an antithetical way.",
        "authors": [
            "Favaretto E",
            "G\u00f6gele M",
            "Bedani F",
            "Giovannini S",
            "Pramstaller PP",
            "Perugi G",
            "Erfurth A",
            "Sani G",
            "Hicks AA",
            "Melotti R"
        ],
        "doi": "10.1016/j.jad.2025.03.055",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "470",
        "volume": "380",
        "issue": "",
        "pages": "162-170",
        "pre": false,
        "pdate": "2025-03-22"
    },
    "10.1038/s41591-025-03827-z": {
        "title": "Polygenic prediction of body mass index and obesity through the life course and across ancestries.",
        "journal": "Nature medicine",
        "year": "2025",
        "abstract": "Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5\u2009years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55\u2009kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.",
        "authors": [
            "Smit RAJ",
            "Wade KH",
            "Hui Q",
            "Arias JD",
            "Yin X",
            "Christiansen MR",
            "Yengo L",
            "Preuss MH",
            "Nakabuye M",
            "Rocheleau G",
            "Graham SE",
            "Buchanan VL",
            "Chittoor G",
            "Graff M",
            "Guindo-Mart\u00ednez M",
            "Lu Y",
            "Marouli E",
            "Sakaue S",
            "Spracklen CN",
            "Vedantam S",
            "Wilson EP",
            "Chen SH",
            "Ferreira T",
            "Ji Y",
            "Karaderi T",
            "L\u00fcll K",
            "Machado M",
            "Malden DE",
            "Medina-Gomez C",
            "Moore A",
            "R\u00fceger S",
            "Akiyama M",
            "Allison MA",
            "Alvarez M",
            "Andersen MK",
            "Appadurai V",
            "Arbeeva L",
            "Bartell E",
            "Bhaskar S",
            "Bielak LF",
            "Bis JC",
            "Bollepalli S",
            "Bork-Jensen J",
            "Bradfield JP",
            "Bradford Y",
            "Brandl C",
            "Braund PS",
            "Brody JA",
            "Broeckel U",
            "Burgdorf KS",
            "Cade BE",
            "Cai Q",
            "Camarda S",
            "Campbell A",
            "Ca\u00f1adas-Garre M",
            "Chai JF",
            "Chesi A",
            "Choi SH",
            "Christofidou P",
            "Couture C",
            "Cuellar-Partida G",
            "Danning R",
            "Degenhardt F",
            "Delgado GE",
            "Delitala A",
            "Demirkan A",
            "Deng X",
            "Dietl A",
            "Dimitriou M",
            "Dimitrov L",
            "Dorajoo R",
            "Eichelmann F",
            "Eliasen AU",
            "Engmann JE",
            "Erdos MR",
            "Fairhurst-Hunter Z",
            "Farmaki AE",
            "Faul JD",
            "Fernandez-Lopez JC",
            "Forer L",
            "Frank M",
            "Freitag-Wolf S",
            "Fritsche LG",
            "Fuchsberger C",
            "Galesloot TE",
            "Gao Y",
            "Geller F",
            "Giannakopoulou O",
            "Giulianini F",
            "Gjesing AP",
            "Goel A",
            "Gordon SD",
            "Gorski M",
            "Grove J",
            "Guo X",
            "Gustafsson S",
            "Haessler J",
            "Hansen TF",
            "Havulinna AS",
            "Haworth SJ",
            "Heard-Costa N",
            "Hemerich D",
            "Highland HM",
            "Hindy G",
            "Ho YL",
            "Hofer E",
            "Holliday E",
            "Horn K",
            "Hornsby WE",
            "Hottenga JJ",
            "Huang H",
            "Huang J",
            "Huerta-Chagoya A",
            "Huo S",
            "Hwang MY",
            "Hwu CM",
            "Iha H",
            "Ikeda DD",
            "Isono M",
            "Jackson AU",
            "Jansen IE",
            "Jiang Y",
            "Johansson I",
            "Jonsson A",
            "J\u00f8rgensen T",
            "Kalafati IP",
            "Kanai M",
            "Kanoni S",
            "K\u00e5rhus LL",
            "Kasturiratne A",
            "Katsuya T",
            "Kawaguchi T",
            "Kember RL",
            "Kentistou KA",
            "Kim D",
            "Kim HN",
            "Kim YJ",
            "Kleber ME",
            "Knol MJ",
            "Kurbasic A",
            "Lauzon M",
            "Le P",
            "Lea R",
            "Lee JY",
            "Lee WJ",
            "Leonard HL",
            "Li H",
            "Li SA",
            "Li X",
            "Li X",
            "Liang J",
            "Lin H",
            "Lin K",
            "Liu J",
            "Liu X",
            "Lo KS",
            "Long J",
            "Lores-Motta L",
            "Luan J",
            "Lyssenko V",
            "Lyytik\u00e4inen LP",
            "Mahajan A",
            "Malik MZ",
            "Mamakou V",
            "Mangino M",
            "Manichaikul A",
            "Marten J",
            "Mattheisen M",
            "McDaid AF",
            "Mei Q",
            "Meiselbach H",
            "Melendez TL",
            "Milaneschi Y",
            "Miller JE",
            "Millwood IY",
            "Mishra PP",
            "Mitchell RE",
            "M\u00f8llehave LT",
            "Mononen N",
            "Mucha S",
            "Munz M",
            "Mykk\u00e4nen J",
            "Nakatochi M",
            "Nardone GG",
            "Nelson CP",
            "Nethander M",
            "Nho CW",
            "Nielsen AA",
            "Nolte IM",
            "Nongmaithem SS",
            "Noordam R",
            "Ntalla I",
            "Nutile T",
            "Pandit A",
            "Pauper M",
            "Petersen ERB",
            "Petersen LV",
            "Piluso F",
            "Pola\u0161ek O",
            "Poveda A",
            "Pyarajan S",
            "Raffield LM",
            "Rakugi H",
            "Ramirez J",
            "Rasheed A",
            "Raven D",
            "Rayner NW",
            "Riveros C",
            "Rohde R",
            "Ruggiero D",
            "Ruotsalainen SE",
            "Ryan KA",
            "Sabater-Lleal M",
            "Santin A",
            "Saxena R",
            "Scholz M",
            "Shen B",
            "Shi J",
            "Shin JH",
            "Sidore C",
            "Sidorenko J",
            "Sim X",
            "Slieker RC",
            "Smith AV",
            "Smith JA",
            "Smyth LJ",
            "Southam L",
            "Steinthorsdottir V",
            "Sun L",
            "Takeuchi F",
            "Taylor KD",
            "Tayo BO",
            "Tcheandjieu C",
            "Terzikhan N",
            "Tesolin P",
            "Teumer A",
            "Theusch E",
            "Thompson DJ",
            "Thorleifsson G",
            "Timmers PRHJ",
            "Trompet S",
            "Turman C",
            "Vaccargiu S",
            "van der Laan SW",
            "van der Most PJ",
            "van Klinken JB",
            "van Setten J",
            "Verma SS",
            "Verweij N",
            "Veturi Y",
            "Wang CA",
            "Wang C",
            "Wang JS",
            "Wang L",
            "Wang YX",
            "Wang Z",
            "Warren HR",
            "Bin Wei W",
            "Wen W",
            "Wheeler WA",
            "Wickremasinghe AR",
            "Wielscher M",
            "Winsvold BS",
            "Wong A",
            "Wuttke M",
            "Xia R",
            "Yamamoto K",
            "Yang J",
            "Yao J",
            "Young H",
            "Yousri NA",
            "Yu L",
            "Zeng L",
            "Zhang W",
            "Zhang X",
            "Zhao JH",
            "Zhao W",
            "Zhou W",
            "Zimmermann ME",
            "Zoledziewska M",
            "'t Hart LM",
            "Adair LS",
            "Adams HHH",
            "Aguilar-Salinas CA",
            "Al-Mulla F",
            "Arnett DK",
            "Asselbergs FW",
            "\u00c5svold BO",
            "Attia J",
            "Banas B",
            "Bandinelli S",
            "Beilin LJ",
            "Bennett DA",
            "Bergler T",
            "Bharadwaj D",
            "Biino G",
            "Boerwinkle E",
            "B\u00f6ger CA",
            "Borja JB",
            "Bouchard C",
            "Bowden DW",
            "Brandslund I",
            "Brumpton B",
            "Buring JE",
            "Caulfield MJ",
            "Chambers JC",
            "Chandak GR",
            "Chanock SJ",
            "Chaturvedi N",
            "Ida Chen YD",
            "Chen Z",
            "Cheng CY",
            "Cho YS",
            "Christensen K",
            "Christophersen IE",
            "Ciullo M",
            "Cole JW",
            "Collins FS",
            "Concas MP",
            "Cooper RS",
            "Cruz M",
            "Cucca F",
            "Cutler MJ",
            "Damrauer SM",
            "Dantoft TM",
            "de Borst GJ",
            "de Geus EJC",
            "de Groot LCPGM",
            "De Jager PL",
            "de Kleijn DPV",
            "de Silva HJ",
            "Dedoussis GV",
            "den Hollander AI",
            "Du S",
            "Easton DF",
            "Eckardt KU",
            "Elders PJM",
            "Eliassen AH",
            "Ellinor PT",
            "Elmst\u00e5hl S",
            "Erdmann J",
            "Evans MK",
            "Fatkin D",
            "Feenstra B",
            "Feitosa MF",
            "Ferrucci L",
            "Florez JC",
            "Ford I",
            "Fornage M",
            "Franke A",
            "Franks PW",
            "Freedman BI",
            "Gieger C",
            "Girotto G",
            "Golightly YM",
            "Gonzalez-Villalpando C",
            "Gordon-Larsen P",
            "Grallert H",
            "Grant SFA",
            "Grarup N",
            "Griffiths L",
            "Gudnason V",
            "Haiman C",
            "Hakonarson H",
            "Hansen T",
            "Hartman CA",
            "Hattersley AT",
            "Hayward C",
            "Heid IM",
            "Heng CK",
            "Hengstenberg C",
            "Herzig KH",
            "Hewitt AW",
            "Hishigaki H",
            "Hougaard DM",
            "Hoyng CB",
            "Huang PL",
            "Huang W",
            "Huang WY",
            "Huffman JE",
            "Hunt SC",
            "Hutri N",
            "Hveem K",
            "Hypp\u00f6nen E",
            "Iacono WG",
            "Ichihara S",
            "Ikram MA",
            "Isasi CR",
            "Jarvelin MR",
            "Jin ZB",
            "J\u00f6ckel KH",
            "Jonas JB",
            "Joshi PK",
            "Jousilahti P",
            "Jukema JW",
            "K\u00e4h\u00f6nen M",
            "Kamatani Y",
            "Kang KD",
            "Kaprio J",
            "Kardia SLR",
            "Karpe F",
            "Kato N",
            "Kavousi M",
            "Kee F",
            "Kessler T",
            "Khera AV",
            "Khor CC",
            "Kiemeney LALM",
            "Kim BJ",
            "Kim EK",
            "Kim HL",
            "Kirchhof P",
            "Kivimaki M",
            "Koh WP",
            "Koistinen HA",
            "Kokkinos A",
            "Kooner JS",
            "Kooperberg C",
            "Kovacs P",
            "Kraaijeveld A",
            "Kraft P",
            "Krauss RM",
            "Kumari M",
            "Kutalik Z",
            "Laakso M",
            "Lange LA",
            "Langenberg C",
            "Launer LJ",
            "Lee H",
            "Lee NR",
            "Lehtim\u00e4ki T",
            "Lemaitre RN",
            "Li H",
            "Li L",
            "Lieb W",
            "Lin X",
            "Lind L",
            "Linneberg A",
            "Liu CT",
            "Liu J",
            "Loeffler M",
            "London B",
            "Lu F",
            "Lubitz SA",
            "Mackey DA",
            "Magnusson PKE",
            "Manson JE",
            "Marcus GM",
            "Marques Vidal P",
            "Martin NG",
            "M\u00e4rz W",
            "Matsuda F",
            "McCarthy MI",
            "McGarrah RW",
            "McGue M",
            "McKnight AJ",
            "Medland SE",
            "Mellstr\u00f6m D",
            "Metspalu A",
            "Mitchell BD",
            "Mitchell P",
            "Mook-Kanamori DO",
            "Mori TA",
            "Morris AD",
            "Mucci LA",
            "Munroe PB",
            "Nalls MA",
            "Nazarian S",
            "Nelson AE",
            "Neville MJ",
            "Newton-Cheh C",
            "Nielsen CS",
            "Niinikoski H",
            "Nikus K",
            "N\u00f6then MM",
            "Ogunniyi A",
            "Ohlsson C",
            "Oldehinkel AJ",
            "Orozco L",
            "Pahkala K",
            "Pajukanta P",
            "Palmer CNA",
            "Parra EJ",
            "Pattaro C",
            "Pedersen O",
            "Pennell CE",
            "Penninx BWJH",
            "Perusse L",
            "Peters A",
            "Peyser PA",
            "Porteous DJ",
            "Posthuma D",
            "Power C",
            "Pramstaller PP",
            "Province MA",
            "Psaty BM",
            "Qi Q",
            "Qu J",
            "Rader DJ",
            "Raitakari OT",
            "Rallidis LS",
            "Rao DC",
            "Redline S",
            "Reilly DF",
            "Reiner AP",
            "Rhee SY",
            "Ridker PM",
            "Rienstra M",
            "Ripatti S",
            "Ritchie MD",
            "Rivadeneira F",
            "Roden DM",
            "Rosendaal FR",
            "Rotter JI",
            "Rudan I",
            "Rutters F",
            "Ryu S",
            "Sabanayagam C",
            "Salako B",
            "Saleheen D",
            "Salomaa V",
            "Samani NJ",
            "Sanghera DK",
            "Sattar N",
            "Schmidt B",
            "Schmidt H",
            "Schmidt R",
            "Schulze MB",
            "Schunkert H",
            "Scott LJ",
            "Scott RJ",
            "Sever P",
            "Sheu WHH",
            "Shoemaker MB",
            "Shu XO",
            "Simonsick EM",
            "Sims M",
            "Singleton AB",
            "Sinner MF",
            "Smith JG",
            "Snieder H",
            "Spector TD",
            "Spedicati B",
            "Stampfer MJ",
            "Stark KJ",
            "Strachan DP",
            "Tabara Y",
            "Tai ES",
            "Tang H",
            "Tardif JC",
            "Thanaraj TA",
            "T\u00f6njes A",
            "Tuomi T",
            "Tuomilehto J",
            "Tusi\u00e9-Luna MT",
            "van Dam RM",
            "van der Harst P",
            "Van der Velde N",
            "van Duijn CM",
            "van Schoor NM",
            "Vitart V",
            "Vohl MC",
            "V\u00f6lker U",
            "Vollenweider P",
            "V\u00f6lzke H",
            "Vrieze S",
            "Wacher-Rodarte NH",
            "Walker M",
            "Wander GS",
            "Wareham NJ",
            "Watanabe RM",
            "Watkins H",
            "Weir DR",
            "Werge TM",
            "Widen E",
            "Willemsen G",
            "Willett WC",
            "Wilson JF",
            "Wilson PWF",
            "Wong TY",
            "Woo JT",
            "Wright AF",
            "Xu H",
            "Yajnik CS",
            "Yang J",
            "Yokota M",
            "Yuan JM",
            "Zeggini E",
            "Zemel BS",
            "Zheng W",
            "Zhu X",
            "Zillikens MC",
            "Zonderman AB",
            "Zwart JA",
            "Abecasis GR",
            "Assimes TL",
            "Auton A",
            "Boehnke M",
            "Chasman DI",
            "Esko T",
            "Stefansson K",
            "Lettre G",
            "Lindgren CM",
            "Ng MCY",
            "O'Donnell CJ",
            "Thorsteinsdottir U",
            "Visscher PM",
            "Walters RG",
            "Winkler TW",
            "Wood AR",
            "Deloukas P",
            "Frayling TM",
            "Justice AE",
            "Kilpel\u00e4inen TO",
            "Locke AE",
            "Mohlke KL",
            "North KE",
            "Okada Y",
            "Willer CJ",
            "Young KL",
            "Fatumo S",
            "McCaffery JM",
            "Timpson NJ",
            "Hirschhorn JN",
            "Sun YV",
            "Berndt SI",
            "Loos RJF"
        ],
        "doi": "10.1038/s41591-025-03827-z",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "461",
        "volume": "31",
        "issue": "9",
        "pages": "3151-3168",
        "pre": false,
        "pdate": "2025-07-22"
    },
    "10.1186/s12863-025-01360-z": {
        "title": "Genome-wide association study meta-analysis uncovers novel genetic variants associated with olfactory dysfunction.",
        "journal": "BMC genomic data",
        "year": "2025",
        "abstract": "**Background**<br> Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA). <br>**Methods**<br> This GWMA included the participants of European ancestry (N\u2009=\u200922,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N\u2009=\u20091,030). Olfactory dysfunction was assessed using a 12-item smell identification test. <br>**Results**<br> GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide polymorphism rs11228623 at the 11q12 locus) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes. <br>**Conclusions**<br> Our findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health. Moreover, these findings could facilitate the identification and monitoring of individuals at increased risk of olfactory dysfunction and associated diseases.",
        "authors": [
            "Imtiaz MA",
            "Melas K",
            "Tin A",
            "Talevi V",
            "Chen H",
            "Fornage M",
            "Shrestha S",
            "G\u00f6gele M",
            "Emmert D",
            "Pattaro C",
            "Pramstaller P",
            "F\u00f6rster F",
            "Horn K",
            "Mosley TH",
            "Fuchsberger C",
            "Scholz M",
            "Breteler MMB",
            "Aziz NA"
        ],
        "doi": "10.1186/s12863-025-01360-z",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "455",
        "volume": "26",
        "issue": "1",
        "pages": "64",
        "pre": false,
        "pdate": "2025-09-18"
    },
    "10.1038/s41467-024-44701-9": {
        "title": "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.",
        "journal": "Nature communications",
        "year": "2024",
        "abstract": "To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total\u00a0T3 and free\u00a0T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free\u00a0T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.",
        "authors": [
            "Sterenborg RBTM",
            "Steinbrenner I",
            "Li Y",
            "Bujnis MN",
            "Naito T",
            "Marouli E",
            "Galesloot TE",
            "Babajide O",
            "Andreasen L",
            "Astrup A",
            "\u00c5svold BO",
            "Bandinelli S",
            "Beekman M",
            "Beilby JP",
            "Bork-Jensen J",
            "Boutin T",
            "Brody JA",
            "Brown SJ",
            "Brumpton B",
            "Campbell PJ",
            "Cappola AR",
            "Ceresini G",
            "Chaker L",
            "Chasman DI",
            "Concas MP",
            "Coutinho de Almeida R",
            "Cross SM",
            "Cucca F",
            "Deary IJ",
            "Kjaergaard AD",
            "Echouffo Tcheugui JB",
            "Ellervik C",
            "Eriksson JG",
            "Ferrucci L",
            "Freudenberg J",
            "Fuchsberger C",
            "Gieger C",
            "Giulianini F",
            "G\u00f6gele M",
            "Graham SE",
            "Grarup N",
            "Gunja\u010da I",
            "Hansen T",
            "Harding BN",
            "Harris SE",
            "Hauns\u00f8 S",
            "Hayward C",
            "Hui J",
            "Ittermann T",
            "Jukema JW",
            "Kajantie E",
            "Kanters JK",
            "K\u00e5rhus LL",
            "Kiemeney LALM",
            "Kloppenburg M",
            "K\u00fchnel B",
            "Lahti J",
            "Langenberg C",
            "Lapauw B",
            "Leese G",
            "Li S",
            "Liewald DCM",
            "Linneberg A",
            "Lominchar JVT",
            "Luan J",
            "Martin NG",
            "Matana A",
            "Meima ME",
            "Meitinger T",
            "Meulenbelt I",
            "Mitchell BD",
            "M\u00f8llehave LT",
            "Mora S",
            "Naitza S",
            "Nauck M",
            "Netea-Maier RT",
            "Noordam R",
            "Nursyifa C",
            "Okada Y",
            "Onano S",
            "Papadopoulou A",
            "Palmer CNA",
            "Pattaro C",
            "Pedersen O",
            "Peters A",
            "Pietzner M",
            "Pola\u0161ek O",
            "Pramstaller PP",
            "Psaty BM",
            "Punda A",
            "Ray D",
            "Redmond P",
            "Richards JB",
            "Ridker PM",
            "Russ TC",
            "Ryan KA",
            "Olesen MS",
            "Schultheiss UT",
            "Selvin E",
            "Siddiqui MK",
            "Sidore C",
            "Slagboom PE",
            "S\u00f8rensen TIA",
            "Soto-Pedre E",
            "Spector TD",
            "Spedicati B",
            "Srinivasan S",
            "Starr JM",
            "Stott DJ",
            "Tanaka T",
            "Torlak V",
            "Trompet S",
            "Tuhkanen J",
            "Uitterlinden AG",
            "van den Akker EB",
            "van den Eynde T",
            "van der Klauw MM",
            "van Heemst D",
            "Verroken C",
            "Visser WE",
            "Vojinovic D",
            "V\u00f6lzke H",
            "Waldenberger M",
            "Walsh JP",
            "Wareham NJ",
            "Weiss S",
            "Willer CJ",
            "Wilson SG",
            "Wolffenbuttel BHR",
            "Wouters HJCM",
            "Wright MJ",
            "Yang Q",
            "Zemunik T",
            "Zhou W",
            "Zhu G",
            "Z\u00f6llner S",
            "Smit JWA",
            "Peeters RP",
            "K\u00f6ttgen A",
            "Teumer A",
            "Medici M"
        ],
        "doi": "10.1038/s41467-024-44701-9",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "449",
        "volume": "15",
        "issue": "1",
        "pages": "888",
        "pre": false,
        "pdate": "2024-01-31"
    },
    "10.1093/ije/dyaf064": {
        "title": "Cohort Profile: the Cooperative Health Research in South Tyrol study.",
        "journal": "International journal of epidemiology",
        "year": "2025",
        "abstract": "The Cooperative Health Research in South Tyrol (CHRIS) cohort was established to study genetic and lifestyle determinants of health and healthy aging in a single administrative district of the alpine Bolzano-South Tyrol province of Italy with a stable population, cooperative administration, shared single reference hospital, relatively homogenous customs and environment, and high healthy life expectancy. <br> A baseline visit at the district reference hospital was completed by 13 393 adults aged \u226518 years (median 46, range 18\u201394, 54% female) in 2011\u20132018, providing socio-demographic, health, lifestyle, and exposure data from self-report questionnaires, interviews, and instrumental examinations, plus urine and blood samples for biobanking, DNA extraction, and molecular characterization (chip genotyping, exome sequencing, metabolomics, proteomics).<br> To date, 4500 baseline participants have completed a visit as part of ongoing follow-up, providing most of the same data and samples as at baseline; additional data collection from wearable activity trackers and on prominent themes like COVID-19 have been introduced. <br> Longitudinal data and biological samples have been collected in the CHRIS study district for over two decades, from 2003, encompassing sociodemographic information, medical history, clinical data, and molecular phenotypes. <br> Dedicated requests for cohort data and samples for research purposes can be submitted via the CHRIS Portal ([https://chrisportal.eurac.edu](https://chrisportal.eurac.edu)).",
        "authors": [
            "Lundin R",
            "Melotti R",
            "Barin L",
            "G\u00f6gele M",
            "Lombardo S",
            "Fanolla A",
            "Zuech P",
            "Rainer J",
            "Emmert D",
            "Fuchsberger C",
            "Mascalzoni D",
            "De Grandi A",
            "Domingues FS",
            "Hicks AA",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1093/ije/dyaf064",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "446",
        "volume": "54",
        "issue": "3",
        "pages": "",
        "pre": false,
        "pdate": "2025-05-29"
    },
    "10.1016/j.ekir.2025.02.018": {
        "title": "Clinical and Metabolic Signatures of FAM47E-SHROOM3 Haplotypes in a General Population Sample.",
        "journal": "Kidney international reports",
        "year": "2025",
        "abstract": "**Introduction**<br> Genome-wide association studies (GWAS) identified a locus on chromosome 4q21.1, spanning the Family With Sequence Similarity 47 Member E *(FAM47E)*, Starch Binding Domain 1 *(STBD1)*, Coiled-Coil Domain Containing 158 *(CCDC158)*, and Shroom Family Member 3 *(SHROOM3)* genes, to be associated with kidney function markers. Functional studies implicated *SHROOM3* as the effector gene, demonstrating its developmental role to guarantee podocyte barrier integrity. However, the locus has also been associated with other clinical traits, including electrolytes, hematological, cardiovascular, and neurological traits, not all of which can be easily traced to the regulation of kidney function. We therefore conducted a systematic analysis of the whole locus' genetic profiles (haplotypes) to assess which phenotypic profiles they were associated with. <br>**Methods**<br> For the 4 genes, we reconstructed haplotypes spanning 71 exonic and intronic variants for 12,834 participants in the Cooperative Health Research in South Tyrol (CHRIS) study based on genotypes imputed on a local whole-exome sequencing (WES) reference panel. Haplotypes were tested for associations with 72 clinical traits, 170 serum metabolites, and 148 plasma protein concentrations, using linear regression models. <br>**Results**<br> We identified 11 haplotypes with a population frequency between 2% and 24%. Compared with the most common haplotype, most haplotypes were associated with higher creatinine-based estimated glomerular filtration rate (eGFR) and lower serum magnesium levels. In addition, specific haplotypes were also associated with biologically diverse groups of traits, including albuminuria, blood pressure, red blood cell traits, carnitines, and amino acids. Cluster analysis highlighted the existence of distinct genetic profiles in which individuals with specific haplotypes presented with specific phenotypic and metabolic signatures. <br>**Conclusion**<br> The genetic variability of the *FAM47E-SHROOM3* locus indicates the existence of population subgroups with distinct biomarker profiles.",
        "authors": [
            "Ghasemi-Semeskandeh D",
            "K\u00f6nig E",
            "Foco L",
            "Dordevic N",
            "G\u00f6gele M",
            "Rainer J",
            "Ralser M",
            "Acoba D",
            "Domingues FS",
            "Peters DJM",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1016/j.ekir.2025.02.018",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "443",
        "volume": "10",
        "issue": "5",
        "pages": "1495-1508",
        "pre": false,
        "pdate": "2025-06-09"
    },
    "10.1038/s42003-024-07115-3": {
        "title": "Novel loci and biomedical consequences of iron homoeostasis variation.",
        "journal": "Communications biology",
        "year": "2024",
        "abstract": "Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression, erythropoiesis, immune response and cellular trafficking. Mendelian randomisation of 292 disease outcomes in 1,492,717 participants revealed associations of iron-related loci and iron status with selected health outcomes across multiple domains. These associations were largely driven by *HFE*, which was associated with the largest iron variation. Our findings enhance understanding of iron homoeostasis and its biomedical consequences, suggesting that lifelong exposure to higher iron levels is likely associated with lower risk of anaemia-related disorders and higher risk of genitourinary, musculoskeletal, infectious and neoplastic diseases.",
        "authors": [
            "Allara E",
            "Bell S",
            "Smith R",
            "Keene SJ",
            "Gill D",
            "Gaziano L",
            "Morselli Gysi D",
            "Wang F",
            "Tragante V",
            "Mason A",
            "Karthikeyan S",
            "Lumbers RT",
            "Bonglack E",
            "Ouwehand W",
            "Roberts DJ",
            "Dowsett J",
            "Ostrowski SR",
            "Larsen MH",
            "Ullum H",
            "Pedersen OB",
            "Brunak S",
            "Banasik K",
            "Erikstrup C",
            "Mitchell J",
            "Fuchsberger C",
            "Pattaro C",
            "Pramstaller PP",
            "Girelli D",
            "Arvas M",
            "Toivonen J",
            "Molnos S",
            "Peters A",
            "Polasek O",
            "Rudan I",
            "Hayward C",
            "McDonnell C",
            "Pirastu N",
            "Wilson JF",
            "van den Hurk K",
            "Quee F",
            "Ferrucci L",
            "Bandinelli S",
            "Tanaka T",
            "Girotto G",
            "Concas MP",
            "Pecori A",
            "Verweij N",
            "van der Harst P",
            "van de Vegte YJ",
            "Kiemeney LA",
            "Sweep FC",
            "Galesloot TE",
            "Sulem P",
            "Gudbjartsson D",
            "Ferkingstad E",
            "Djousse L",
            "Cho K",
            "Inouye M",
            "Burgess S",
            "Benyamin B",
            "Oexle K",
            "Swinkels D",
            "Stefansson K",
            "Magnusson M",
            "Ganna A",
            "Gaziano M",
            "Ivey K",
            "Danesh J",
            "Pereira A",
            "Wood AM",
            "Butterworth AS",
            "Di Angelantonio E"
        ],
        "doi": "10.1038/s42003-024-07115-3",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "433",
        "volume": "7",
        "issue": "1",
        "pages": "1631",
        "pre": false,
        "pdate": "2024-12-07"
    },
    "10.1038/s41586-021-03767-x": {
        "title": "Mapping the human genetic architecture of COVID-19.",
        "journal": "Nature",
        "year": "2021",
        "abstract": "The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.",
        "authors": [
            "COVID-19 Host Genetics Initiative"
        ],
        "doi": "10.1038/s41586-021-03767-x",
        "source_study": [
            "CHRIS COVID-19"
        ],
        "ar": "409",
        "volume": "600",
        "issue": "7889",
        "pages": "472-477",
        "pre": false,
        "pdate": "2021-07-09"
    },
    "10.1038/nrg3218": {
        "title": "From patients to partners: participant-centric initiatives in biomedical research.",
        "journal": "Nature reviews. Genetics",
        "year": "2012",
        "abstract": "Advances in computing technology and bioinformatics mean that medical research is increasingly characterized by large international consortia of researchers that are reliant on large data sets and biobanks. These trends raise a number of challenges for obtaining consent, protecting participant privacy concerns and maintaining public trust. Participant-centred initiatives (PCIs) use social media technologies to address these immediate concerns, but they also provide the basis for long-term interactive partnerships. Here, we give an overview of this rapidly moving field by providing an analysis of the different PCI approaches, as well as the benefits and challenges of implementing PCIs.",
        "authors": [
            "Kaye J",
            "Curren L",
            "Anderson N",
            "Edwards K",
            "Fullerton SM",
            "Kanellopoulou N",
            "Lund D",
            "MacArthur DG",
            "Mascalzoni D",
            "Shepherd J",
            "Taylor PL",
            "Terry SF",
            "Winter SF"
        ],
        "doi": "10.1038/nrg3218",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "430",
        "volume": "13",
        "issue": "5",
        "pages": "371-6",
        "pre": false,
        "pdate": "2012-04-05"
    },
    "10.1161/JAHA.123.034760": {
        "title": "Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125\u2009393 Participants.",
        "journal": "Journal of the American Heart Association",
        "year": "2024",
        "abstract": "**Background**<br> Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. <br>**Methods and results**<br>We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62\u2009532] and replication [N=59\u2009861] of lead variants) and a single-stage genome-wide meta-analysis (N=122\u2009393, [European ancestry N=117\u2009581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5\u00d710<sup>-8</sup>). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (*SPPL2B* and *RFX6*). <br>**Conclusions**<br> We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors\u00a0including rare variation and other environmental interactions need to be considered.",
        "authors": [
            "Young WJ",
            "van der Most PJ",
            "Bartz TM",
            "Bos MM",
            "Biino G",
            "Duong T",
            "Foco L",
            "Lominchar JT",
            "M\u00fcller-Nurasyid M",
            "Nardone GG",
            "Pecori A",
            "Ramirez J",
            "Repetto L",
            "Schramm K",
            "Shen X",
            "van Duijvenboden S",
            "van Heemst D",
            "Weiss S",
            "Yao J",
            "Benjamins JW",
            "Alonso A",
            "Spedicati B",
            "Biggs ML",
            "Brody JA",
            "D\u00f6rr M",
            "Fuchsberger C",
            "G\u00f6gele M",
            "Guo X",
            "Ikram MA",
            "Jukema JW",
            "K\u00e4\u00e4b S",
            "Kanters JK",
            "Lin HJ",
            "Linneberg A",
            "Nauck M",
            "Nolte IM",
            "Pianigiani G",
            "Santin A",
            "Soliman EZ",
            "Tesolin P",
            "Vaccargiu S",
            "Waldenberger M",
            "van der Harst P",
            "Verweij N",
            "Arking DE",
            "Concas MP",
            "De Grandi A",
            "Girotto G",
            "Grarup N",
            "Kavousi M",
            "Mook-Kanamori DO",
            "Navarro P",
            "Orini M",
            "Padmanabhan S",
            "Pattaro C",
            "Peters A",
            "Pirastu M",
            "Pramstaller PP",
            "Heckbert SR",
            "Sinner M",
            "Snieder H",
            "V\u00f6lker U",
            "Wilson JF",
            "Gauderman WJ",
            "Lambiase PD",
            "Sotoodehnia N",
            "Tinker A",
            "Warren HR",
            "Noordam R",
            "Munroe PB"
        ],
        "doi": "10.1161/JAHA.123.034760",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "429",
        "volume": "13",
        "issue": "17",
        "pages": "e034760",
        "pre": false,
        "pdate": "2024-08-31"
    },
    "10.1007/s12687-024-00733-8": {
        "title": "How to communicate and what to disclose to participants in a recall-by-genotype research approach: a multistep empirical study.",
        "journal": "Journal of community genetics",
        "year": "2024",
        "abstract": "Recall-by-genotype (RbG) is a bottom-up approach using existing genetic data to design follow-up stratified studies. Genetic information may be partially disclosed at invitation, thus raising ethical issues which call for defined best practices for disclosure and communication in RbG approaches. Within the context of the ProtectMove sub-project of the Cooperative Health Research in South Tyrol (CHRIS) study, we investigated research participant perspectives on RbG communication strategies (Step 1 and 4, questionnaire with a subsample of CHRIS participants with and without previous experience of RbG, respectively). Additionally, we explored researchers' and study personnel's experience with RbG (Step 2 and 3, focus group discussion). In step 1 (N\u2009=\u200995), participants were generally satisfied with the study process. Most (71.6%) wanted to know their carrier status for personal and collective benefit. Tailored disclosure strategies and transparent, effective, and well-thought-out communication approaches were advocated by study personnel (Step 2, N\u2009=\u20096) and researchers (Step 3, N\u2009=\u20097). Challenges in dealing with uncertainty, concerns caused by RbG invitations, and the possibility of misunderstanding were also raised. In step 4 (N\u2009=\u2009369), participants valued being informed of study details at the first invitation stage, and generally felt comfortable towards RbG study invitations (58.5%) and to receiving genetic information after the study (58.5-81.6%). Comfort and perceived impact of disclosure of genetic information varied according to the type of variant being potentially disclosed. This study suggested designing communication strategies, based on clear and understandable explanations, sensitive to participant expectations and preferences, developing case-by-case solutions for disclosure.",
        "authors": [
            "Tschigg K",
            "Consoli L",
            "Br\u00fcggemann N",
            "Hicks AA",
            "Staunton C",
            "Mascalzoni D",
            "Biasiotto R"
        ],
        "doi": "10.1007/s12687-024-00733-8",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "428",
        "volume": "15",
        "issue": "6",
        "pages": "615-630",
        "pre": false,
        "pdate": "2024-09-26"
    },
    "10.1242/dmm.044727": {
        "title": "Silencing of CCR4-NOT complex subunits affects heart structure and function.",
        "journal": "Disease models & mechanisms",
        "year": "2020",
        "abstract": "The identification of genetic variants that predispose individuals to cardiovascular disease and a better understanding of their targets would be highly advantageous. Genome-wide association studies have identified variants that associate with QT-interval length (a measure of myocardial repolarization). Three of the strongest associating variants (single-nucleotide polymorphisms) are located in the putative promotor region of *CNOT1*, a gene encoding the central CNOT1 subunit of CCR4-NOT: a multifunctional, conserved complex regulating gene expression and mRNA stability and turnover. We isolated the minimum fragment of the *CNOT1* promoter containing all three variants from individuals homozygous for the QT risk alleles and demonstrated that the haplotype associating with longer QT interval caused reduced reporter expression in a cardiac cell line, suggesting that reduced *CNOT1* expression might contribute to abnormal QT intervals. Systematic siRNA-mediated knockdown of CCR4-NOT components in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) revealed that silencing *CNOT1* and other CCR4-NOT genes reduced their proliferative capacity. Silencing *CNOT7* also shortened action potential duration. Furthermore, the cardiac-specific knockdown of *Drosophila* orthologs of CCR4-NOT genes *in vivo* (*CNOT1*/*Not1* and *CNOT7*/*8*/*Pop2*) was either lethal or resulted in dilated cardiomyopathy, reduced contractility or a propensity for arrhythmia. Silencing *CNOT2*/*Not2*, *CNOT4*/*Not4* and *CNOT6*/*6L*/*twin* also affected cardiac chamber size and contractility. Developmental studies suggested that *CNOT1*/*Not1* and *CNOT7*/*8*/*Pop2* are required during cardiac remodeling from larval to adult stages. To summarize, we have demonstrated how disease-associated genes identified by GWAS can be investigated by combining human cardiomyocyte cell-based and whole-organism *in vivo* heart models. Our results also suggest a potential link of *CNOT1* and *CNOT7*/*8* to QT alterations and further establish a crucial role of the CCR4-NOT complex in heart development and function.This article has an associated First Person interview with the first author of the paper.",
        "authors": [
            "Elm\u00e9n L",
            "Volpato CB",
            "Kervadec A",
            "Pineda S",
            "Kalvakuri S",
            "Alayari NN",
            "Foco L",
            "Pramstaller PP",
            "Ocorr K",
            "Rossini A",
            "Cammarato A",
            "Colas AR",
            "Hicks AA",
            "Bodmer R"
        ],
        "doi": "10.1242/dmm.044727",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "427",
        "volume": "13",
        "issue": "7",
        "pages": "",
        "pre": false,
        "pdate": "2020-05-31"
    },
    "10.1016/j.ajhg.2022.06.012": {
        "title": "A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.",
        "journal": "American journal of human genetics",
        "year": "2022",
        "abstract": "A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, *CREBRF* and *RRBP1*, which show convergent evidence across functional datasets supporting their roles in lipid biology.",
        "authors": [
            "Ramdas S",
            "Judd J",
            "Graham SE",
            "Kanoni S",
            "Wang Y",
            "Surakka I",
            "Wenz B",
            "Clarke SL",
            "Chesi A",
            "Wells A",
            "Bhatti KF",
            "Vedantam S",
            "Winkler TW",
            "Locke AE",
            "Marouli E",
            "Zajac GJM",
            "Wu KH",
            "Ntalla I",
            "Hui Q",
            "Klarin D",
            "Hilliard AT",
            "Wang Z",
            "Xue C",
            "Thorleifsson G",
            "Helgadottir A",
            "Gudbjartsson DF",
            "Holm H",
            "Olafsson I",
            "Hwang MY",
            "Han S",
            "Akiyama M",
            "Sakaue S",
            "Terao C",
            "Kanai M",
            "Zhou W",
            "Brumpton BM",
            "Rasheed H",
            "Havulinna AS",
            "Veturi Y",
            "Pacheco JA",
            "Rosenthal EA",
            "Lingren T",
            "Feng Q",
            "Kullo IJ",
            "Narita A",
            "Takayama J",
            "Martin HC",
            "Hunt KA",
            "Trivedi B",
            "Haessler J",
            "Giulianini F",
            "Bradford Y",
            "Miller JE",
            "Campbell A",
            "Lin K",
            "Millwood IY",
            "Rasheed A",
            "Hindy G",
            "Faul JD",
            "Zhao W",
            "Weir DR",
            "Turman C",
            "Huang H",
            "Graff M",
            "Choudhury A",
            "Sengupta D",
            "Mahajan A",
            "Brown MR",
            "Zhang W",
            "Yu K",
            "Schmidt EM",
            "Pandit A",
            "Gustafsson S",
            "Yin X",
            "Luan J",
            "Zhao JH",
            "Matsuda F",
            "Jang HM",
            "Yoon K",
            "Medina-Gomez C",
            "Pitsillides A",
            "Hottenga JJ",
            "Wood AR",
            "Ji Y",
            "Gao Z",
            "Haworth S",
            "Mitchell RE",
            "Chai JF",
            "Aadahl M",
            "Bjerregaard AA",
            "Yao J",
            "Manichaikul A",
            "Lee WJ",
            "Hsiung CA",
            "Warren HR",
            "Ramirez J",
            "Bork-Jensen J",
            "K\u00e5rhus LL",
            "Goel A",
            "Sabater-Lleal M",
            "Noordam R",
            "Mauro P",
            "Matteo F",
            "McDaid AF",
            "Marques-Vidal P",
            "Wielscher M",
            "Trompet S",
            "Sattar N",
            "M\u00f8llehave LT",
            "Munz M",
            "Zeng L",
            "Huang J",
            "Yang B",
            "Poveda A",
            "Kurbasic A",
            "Sch\u00f6nherr S",
            "Forer L",
            "Scholz M",
            "Galesloot TE",
            "Bradfield JP",
            "Ruotsalainen SE",
            "Daw EW",
            "Zmuda JM",
            "Mitchell JS",
            "Fuchsberger C",
            "Christensen H",
            "Brody JA",
            "Le P",
            "Feitosa MF",
            "Wojczynski MK",
            "Hemerich D",
            "Preuss M",
            "Mangino M",
            "Christofidou P",
            "Verweij N",
            "Benjamins JW",
            "Engmann J",
            "Noah TL",
            "Verma A",
            "Slieker RC",
            "Lo KS",
            "Zilhao NR",
            "Kleber ME",
            "Delgado GE",
            "Huo S",
            "Ikeda DD",
            "Iha H",
            "Yang J",
            "Liu J",
            "Demirkan A",
            "Leonard HL",
            "Marten J",
            "Emmel C",
            "Schmidt B",
            "Smyth LJ",
            "Ca\u00f1adas-Garre M",
            "Wang C",
            "Nakatochi M",
            "Wong A",
            "Hutri-K\u00e4h\u00f6nen N",
            "Sim X",
            "Xia R",
            "Huerta-Chagoya A",
            "Fernandez-Lopez JC",
            "Lyssenko V",
            "Nongmaithem SS",
            "Sankareswaran A",
            "Irvin MR",
            "Oldmeadow C",
            "Kim HN",
            "Ryu S",
            "Timmers PRHJ",
            "Arbeeva L",
            "Dorajoo R",
            "Lange LA",
            "Prasad G",
            "Lor\u00e9s-Motta L",
            "Pauper M",
            "Long J",
            "Li X",
            "Theusch E",
            "Takeuchi F",
            "Spracklen CN",
            "Loukola A",
            "Bollepalli S",
            "Warner SC",
            "Wang YX",
            "Wei WB",
            "Nutile T",
            "Ruggiero D",
            "Sung YJ",
            "Chen S",
            "Liu F",
            "Yang J",
            "Kentistou KA",
            "Banas B",
            "Morgan A",
            "Meidtner K",
            "Bielak LF",
            "Smith JA",
            "Hebbar P",
            "Farmaki AE",
            "Hofer E",
            "Lin M",
            "Concas MP",
            "Vaccargiu S",
            "van der Most PJ",
            "Pitk\u00e4nen N",
            "Cade BE",
            "van der Laan SW",
            "Chitrala KN",
            "Weiss S",
            "Bentley AR",
            "Doumatey AP",
            "Adeyemo AA",
            "Lee JY",
            "Petersen ERB",
            "Nielsen AA",
            "Choi HS",
            "Nethander M",
            "Freitag-Wolf S",
            "Southam L",
            "Rayner NW",
            "Wang CA",
            "Lin SY",
            "Wang JS",
            "Couture C",
            "Lyytik\u00e4inen LP",
            "Nikus K",
            "Cuellar-Partida G",
            "Vestergaard H",
            "Hidalgo B",
            "Giannakopoulou O",
            "Cai Q",
            "Obura MO",
            "van Setten J",
            "He KY",
            "Tang H",
            "Terzikhan N",
            "Shin JH",
            "Jackson RD",
            "Reiner AP",
            "Martin LW",
            "Chen Z",
            "Li L",
            "Kawaguchi T",
            "Thiery J",
            "Bis JC",
            "Launer LJ",
            "Li H",
            "Nalls MA",
            "Raitakari OT",
            "Ichihara S",
            "Wild SH",
            "Nelson CP",
            "Campbell H",
            "J\u00e4ger S",
            "Nabika T",
            "Al-Mulla F",
            "Niinikoski H",
            "Braund PS",
            "Kolcic I",
            "Kovacs P",
            "Giardoglou T",
            "Katsuya T",
            "de Kleijn D",
            "de Borst GJ",
            "Kim EK",
            "Adams HHH",
            "Ikram MA",
            "Zhu X",
            "Asselbergs FW",
            "Kraaijeveld AO",
            "Beulens JWJ",
            "Shu XO",
            "Rallidis LS",
            "Pedersen O",
            "Hansen T",
            "Mitchell P",
            "Hewitt AW",
            "K\u00e4h\u00f6nen M",
            "P\u00e9russe L",
            "Bouchard C",
            "T\u00f6njes A",
            "Ida Chen YD",
            "Pennell CE",
            "Mori TA",
            "Lieb W",
            "Franke A",
            "Ohlsson C",
            "Mellstr\u00f6m D",
            "Cho YS",
            "Lee H",
            "Yuan JM",
            "Koh WP",
            "Rhee SY",
            "Woo JT",
            "Heid IM",
            "Stark KJ",
            "Zimmermann ME",
            "V\u00f6lzke H",
            "Homuth G",
            "Evans MK",
            "Zonderman AB",
            "Polasek O",
            "Pasterkamp G",
            "Hoefer IE",
            "Redline S",
            "Pahkala K",
            "Oldehinkel AJ",
            "Snieder H",
            "Biino G",
            "Schmidt R",
            "Schmidt H",
            "Bandinelli S",
            "Dedoussis G",
            "Thanaraj TA",
            "Peyser PA",
            "Kato N",
            "Schulze MB",
            "Girotto G",
            "B\u00f6ger CA",
            "Jung B",
            "Joshi PK",
            "Bennett DA",
            "De Jager PL",
            "Lu X",
            "Mamakou V",
            "Brown M",
            "Caulfield MJ",
            "Munroe PB",
            "Guo X",
            "Ciullo M",
            "Jonas JB",
            "Samani NJ",
            "Kaprio J",
            "Pajukanta P",
            "Tusi\u00e9-Luna T",
            "Aguilar-Salinas CA",
            "Adair LS",
            "Bechayda SA",
            "de Silva HJ",
            "Wickremasinghe AR",
            "Krauss RM",
            "Wu JY",
            "Zheng W",
            "den Hollander AI",
            "Bharadwaj D",
            "Correa A",
            "Wilson JG",
            "Lind L",
            "Heng CK",
            "Nelson AE",
            "Golightly YM",
            "Wilson JF",
            "Penninx B",
            "Kim HL",
            "Attia J",
            "Scott RJ",
            "Rao DC",
            "Arnett DK",
            "Walker M",
            "Scott LJ",
            "Koistinen HA",
            "Chandak GR",
            "Mercader JM",
            "Villalpando CG",
            "Orozco L",
            "Fornage M",
            "Tai ES",
            "van Dam RM",
            "Lehtim\u00e4ki T",
            "Chaturvedi N",
            "Yokota M",
            "Liu J",
            "Reilly DF",
            "McKnight AJ",
            "Kee F",
            "J\u00f6ckel KH",
            "McCarthy MI",
            "Palmer CNA",
            "Vitart V",
            "Hayward C",
            "Simonsick E",
            "van Duijn CM",
            "Jin ZB",
            "Lu F",
            "Hishigaki H",
            "Lin X",
            "M\u00e4rz W",
            "Gudnason V",
            "Tardif JC",
            "Lettre G",
            "T Hart LM",
            "Elders PJM",
            "Rader DJ",
            "Damrauer SM",
            "Kumari M",
            "Kivimaki M",
            "van der Harst P",
            "Spector TD",
            "Loos RJF",
            "Province MA",
            "Parra EJ",
            "Cruz M",
            "Psaty BM",
            "Brandslund I",
            "Pramstaller PP",
            "Rotimi CN",
            "Christensen K",
            "Ripatti S",
            "Wid\u00e9n E",
            "Hakonarson H",
            "Grant SFA",
            "Kiemeney L",
            "de Graaf J",
            "Loeffler M",
            "Kronenberg F",
            "Gu D",
            "Erdmann J",
            "Schunkert H",
            "Franks PW",
            "Linneberg A",
            "Jukema JW",
            "Khera AV",
            "M\u00e4nnikk\u00f6 M",
            "Jarvelin MR",
            "Kutalik Z",
            "Francesco C",
            "Mook-Kanamori DO",
            "Willems van Dijk K",
            "Watkins H",
            "Strachan DP",
            "Grarup N",
            "Sever P",
            "Poulter N",
            "Huey-Herng Sheu W",
            "Rotter JI",
            "Dantoft TM",
            "Karpe F",
            "Neville MJ",
            "Timpson NJ",
            "Cheng CY",
            "Wong TY",
            "Khor CC",
            "Li H",
            "Sabanayagam C",
            "Peters A",
            "Gieger C",
            "Hattersley AT",
            "Pedersen NL",
            "Magnusson PKE",
            "Boomsma DI",
            "de Geus EJC",
            "Cupples LA",
            "van Meurs JBJ",
            "Ikram A",
            "Ghanbari M",
            "Gordon-Larsen P",
            "Huang W",
            "Kim YJ",
            "Tabara Y",
            "Wareham NJ",
            "Langenberg C",
            "Zeggini E",
            "Tuomilehto J",
            "Kuusisto J",
            "Laakso M",
            "Ingelsson E",
            "Abecasis G",
            "Chambers JC",
            "Kooner JS",
            "de Vries PS",
            "Morrison AC",
            "Hazelhurst S",
            "Ramsay M",
            "North KE",
            "Daviglus M",
            "Kraft P",
            "Martin NG",
            "Whitfield JB",
            "Abbas S",
            "Saleheen D",
            "Walters RG",
            "Holmes MV",
            "Black C",
            "Smith BH",
            "Baras A",
            "Justice AE",
            "Buring JE",
            "Ridker PM",
            "Chasman DI",
            "Kooperberg C",
            "Tamiya G",
            "Yamamoto M",
            "van Heel DA",
            "Trembath RC",
            "Wei WQ",
            "Jarvik GP",
            "Namjou B",
            "Hayes MG",
            "Ritchie MD",
            "Jousilahti P",
            "Salomaa V",
            "Hveem K",
            "\u00c5svold BO",
            "Kubo M",
            "Kamatani Y",
            "Okada Y",
            "Murakami Y",
            "Kim BJ",
            "Thorsteinsdottir U",
            "Stefansson K",
            "Zhang J",
            "Chen YE",
            "Ho YL",
            "Lynch JA",
            "Tsao PS",
            "Chang KM",
            "Cho K",
            "O'Donnell CJ",
            "Gaziano JM",
            "Wilson P",
            "Mohlke KL",
            "Frayling TM",
            "Hirschhorn JN",
            "Kathiresan S",
            "Boehnke M",
            "Struan Grant",
            "Natarajan P",
            "Sun YV",
            "Morris AP",
            "Deloukas P",
            "Peloso G",
            "Assimes TL",
            "Willer CJ",
            "Zhu X",
            "Brown CD"
        ],
        "doi": "10.1016/j.ajhg.2022.06.012",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "423",
        "volume": "109",
        "issue": "8",
        "pages": "1366-1387",
        "pre": false,
        "pdate": "2022-08-06"
    },
    "10.1186/s13059-022-02837-1": {
        "title": "Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.",
        "journal": "Genome biology",
        "year": "2022",
        "abstract": "**Background**<br> Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. <br>**Results**<br> To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N\u2009=\u20091,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. <br>**Conclusions**<br> Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.",
        "authors": [
            "Kanoni S",
            "Graham SE",
            "Wang Y",
            "Surakka I",
            "Ramdas S",
            "Zhu X",
            "Clarke SL",
            "Bhatti KF",
            "Vedantam S",
            "Winkler TW",
            "Locke AE",
            "Marouli E",
            "Zajac GJM",
            "Wu KH",
            "Ntalla I",
            "Hui Q",
            "Klarin D",
            "Hilliard AT",
            "Wang Z",
            "Xue C",
            "Thorleifsson G",
            "Helgadottir A",
            "Gudbjartsson DF",
            "Holm H",
            "Olafsson I",
            "Hwang MY",
            "Han S",
            "Akiyama M",
            "Sakaue S",
            "Terao C",
            "Kanai M",
            "Zhou W",
            "Brumpton BM",
            "Rasheed H",
            "Havulinna AS",
            "Veturi Y",
            "Pacheco JA",
            "Rosenthal EA",
            "Lingren T",
            "Feng Q",
            "Kullo IJ",
            "Narita A",
            "Takayama J",
            "Martin HC",
            "Hunt KA",
            "Trivedi B",
            "Haessler J",
            "Giulianini F",
            "Bradford Y",
            "Miller JE",
            "Campbell A",
            "Lin K",
            "Millwood IY",
            "Rasheed A",
            "Hindy G",
            "Faul JD",
            "Zhao W",
            "Weir DR",
            "Turman C",
            "Huang H",
            "Graff M",
            "Choudhury A",
            "Sengupta D",
            "Mahajan A",
            "Brown MR",
            "Zhang W",
            "Yu K",
            "Schmidt EM",
            "Pandit A",
            "Gustafsson S",
            "Yin X",
            "Luan J",
            "Zhao JH",
            "Matsuda F",
            "Jang HM",
            "Yoon K",
            "Medina-Gomez C",
            "Pitsillides A",
            "Hottenga JJ",
            "Wood AR",
            "Ji Y",
            "Gao Z",
            "Haworth S",
            "Yousri NA",
            "Mitchell RE",
            "Chai JF",
            "Aadahl M",
            "Bjerregaard AA",
            "Yao J",
            "Manichaikul A",
            "Hwu CM",
            "Hung YJ",
            "Warren HR",
            "Ramirez J",
            "Bork-Jensen J",
            "K\u00e5rhus LL",
            "Goel A",
            "Sabater-Lleal M",
            "Noordam R",
            "Mauro P",
            "Matteo F",
            "McDaid AF",
            "Marques-Vidal P",
            "Wielscher M",
            "Trompet S",
            "Sattar N",
            "M\u00f8llehave LT",
            "Munz M",
            "Zeng L",
            "Huang J",
            "Yang B",
            "Poveda A",
            "Kurbasic A",
            "Lamina C",
            "Forer L",
            "Scholz M",
            "Galesloot TE",
            "Bradfield JP",
            "Ruotsalainen SE",
            "Daw E",
            "Zmuda JM",
            "Mitchell JS",
            "Fuchsberger C",
            "Christensen H",
            "Brody JA",
            "Vazquez-Moreno M",
            "Feitosa MF",
            "Wojczynski MK",
            "Wang Z",
            "Preuss MH",
            "Mangino M",
            "Christofidou P",
            "Verweij N",
            "Benjamins JW",
            "Engmann J",
            "Tsao NL",
            "Verma A",
            "Slieker RC",
            "Lo KS",
            "Zilhao NR",
            "Le P",
            "Kleber ME",
            "Delgado GE",
            "Huo S",
            "Ikeda DD",
            "Iha H",
            "Yang J",
            "Liu J",
            "Demirkan A",
            "Leonard HL",
            "Marten J",
            "Frank M",
            "Schmidt B",
            "Smyth LJ",
            "Ca\u00f1adas-Garre M",
            "Wang C",
            "Nakatochi M",
            "Wong A",
            "Hutri-K\u00e4h\u00f6nen N",
            "Sim X",
            "Xia R",
            "Huerta-Chagoya A",
            "Fernandez-Lopez JC",
            "Lyssenko V",
            "Nongmaithem SS",
            "Bayyana S",
            "Stringham HM",
            "Irvin MR",
            "Oldmeadow C",
            "Kim HN",
            "Ryu S",
            "Timmers PRHJ",
            "Arbeeva L",
            "Dorajoo R",
            "Lange LA",
            "Prasad G",
            "Lor\u00e9s-Motta L",
            "Pauper M",
            "Long J",
            "Li X",
            "Theusch E",
            "Takeuchi F",
            "Spracklen CN",
            "Loukola A",
            "Bollepalli S",
            "Warner SC",
            "Wang YX",
            "Wei WB",
            "Nutile T",
            "Ruggiero D",
            "Sung YJ",
            "Chen S",
            "Liu F",
            "Yang J",
            "Kentistou KA",
            "Banas B",
            "Nardone GG",
            "Meidtner K",
            "Bielak LF",
            "Smith JA",
            "Hebbar P",
            "Farmaki AE",
            "Hofer E",
            "Lin M",
            "Concas MP",
            "Vaccargiu S",
            "van der Most PJ",
            "Pitk\u00e4nen N",
            "Cade BE",
            "van der Laan SW",
            "Chitrala KN",
            "Weiss S",
            "Bentley AR",
            "Doumatey AP",
            "Adeyemo AA",
            "Lee JY",
            "Petersen ERB",
            "Nielsen AA",
            "Choi HS",
            "Nethander M",
            "Freitag-Wolf S",
            "Southam L",
            "Rayner NW",
            "Wang CA",
            "Lin SY",
            "Wang JS",
            "Couture C",
            "Lyytik\u00e4inen LP",
            "Nikus K",
            "Cuellar-Partida G",
            "Vestergaard H",
            "Hidalgo B",
            "Giannakopoulou O",
            "Cai Q",
            "Obura MO",
            "van Setten J",
            "Li X",
            "Liang J",
            "Tang H",
            "Terzikhan N",
            "Shin JH",
            "Jackson RD",
            "Reiner AP",
            "Martin LW",
            "Chen Z",
            "Li L",
            "Kawaguchi T",
            "Thiery J",
            "Bis JC",
            "Launer LJ",
            "Li H",
            "Nalls MA",
            "Raitakari OT",
            "Ichihara S",
            "Wild SH",
            "Nelson CP",
            "Campbell H",
            "J\u00e4ger S",
            "Nabika T",
            "Al-Mulla F",
            "Niinikoski H",
            "Braund PS",
            "Kolcic I",
            "Kovacs P",
            "Giardoglou T",
            "Katsuya T",
            "de Kleijn D",
            "de Borst GJ",
            "Kim EK",
            "Adams HHH",
            "Ikram MA",
            "Zhu X",
            "Asselbergs FW",
            "Kraaijeveld AO",
            "Beulens JWJ",
            "Shu XO",
            "Rallidis LS",
            "Pedersen O",
            "Hansen T",
            "Mitchell P",
            "Hewitt AW",
            "K\u00e4h\u00f6nen M",
            "P\u00e9russe L",
            "Bouchard C",
            "T\u00f6njes A",
            "Chen YI",
            "Pennell CE",
            "Mori TA",
            "Lieb W",
            "Franke A",
            "Ohlsson C",
            "Mellstr\u00f6m D",
            "Cho YS",
            "Lee H",
            "Yuan JM",
            "Koh WP",
            "Rhee SY",
            "Woo JT",
            "Heid IM",
            "Stark KJ",
            "Zimmermann ME",
            "V\u00f6lzke H",
            "Homuth G",
            "Evans MK",
            "Zonderman AB",
            "Polasek O",
            "Pasterkamp G",
            "Hoefer IE",
            "Redline S",
            "Pahkala K",
            "Oldehinkel AJ",
            "Snieder H",
            "Biino G",
            "Schmidt R",
            "Schmidt H",
            "Bandinelli S",
            "Dedoussis G",
            "Thanaraj TA",
            "Kardia SLR",
            "Peyser PA",
            "Kato N",
            "Schulze MB",
            "Girotto G",
            "B\u00f6ger CA",
            "Jung B",
            "Joshi PK",
            "Bennett DA",
            "De Jager PL",
            "Lu X",
            "Mamakou V",
            "Brown M",
            "Caulfield MJ",
            "Munroe PB",
            "Guo X",
            "Ciullo M",
            "Jonas JB",
            "Samani NJ",
            "Kaprio J",
            "Pajukanta P",
            "Tusi\u00e9-Luna T",
            "Aguilar-Salinas CA",
            "Adair LS",
            "Bechayda SA",
            "de Silva HJ",
            "Wickremasinghe AR",
            "Krauss RM",
            "Wu JY",
            "Zheng W",
            "Hollander AI",
            "Bharadwaj D",
            "Correa A",
            "Wilson JG",
            "Lind L",
            "Heng CK",
            "Nelson AE",
            "Golightly YM",
            "Wilson JF",
            "Penninx B",
            "Kim HL",
            "Attia J",
            "Scott RJ",
            "Rao DC",
            "Arnett DK",
            "Hunt SC",
            "Walker M",
            "Koistinen HA",
            "Chandak GR",
            "Mercader JM",
            "Costanzo MC",
            "Jang D",
            "Burtt NP",
            "Villalpando CG",
            "Orozco L",
            "Fornage M",
            "Tai E",
            "van Dam RM",
            "Lehtim\u00e4ki T",
            "Chaturvedi N",
            "Yokota M",
            "Liu J",
            "Reilly DF",
            "McKnight AJ",
            "Kee F",
            "J\u00f6ckel KH",
            "McCarthy MI",
            "Palmer CNA",
            "Vitart V",
            "Hayward C",
            "Simonsick E",
            "van Duijn CM",
            "Jin ZB",
            "Qu J",
            "Hishigaki H",
            "Lin X",
            "M\u00e4rz W",
            "Gudnason V",
            "Tardif JC",
            "Lettre G",
            "Hart LM'",
            "Elders PJM",
            "Damrauer SM",
            "Kumari M",
            "Kivimaki M",
            "van der Harst P",
            "Spector TD",
            "Loos RJF",
            "Province MA",
            "Parra EJ",
            "Cruz M",
            "Psaty BM",
            "Brandslund I",
            "Pramstaller PP",
            "Rotimi CN",
            "Christensen K",
            "Ripatti S",
            "Wid\u00e9n E",
            "Hakonarson H",
            "Grant SFA",
            "Kiemeney LALM",
            "de Graaf J",
            "Loeffler M",
            "Kronenberg F",
            "Gu D",
            "Erdmann J",
            "Schunkert H",
            "Franks PW",
            "Linneberg A",
            "Jukema JW",
            "Khera AV",
            "M\u00e4nnikk\u00f6 M",
            "Jarvelin MR",
            "Kutalik Z",
            "Francesco C",
            "Mook-Kanamori DO",
            "van Dijk KW",
            "Watkins H",
            "Strachan DP",
            "Grarup N",
            "Sever P",
            "Poulter N",
            "Chuang LM",
            "Rotter JI",
            "Dantoft TM",
            "Karpe F",
            "Neville MJ",
            "Timpson NJ",
            "Cheng CY",
            "Wong TY",
            "Khor CC",
            "Li H",
            "Sabanayagam C",
            "Peters A",
            "Gieger C",
            "Hattersley AT",
            "Pedersen NL",
            "Magnusson PKE",
            "Boomsma DI",
            "Willemsen AHM",
            "Cupples L",
            "van Meurs JBJ",
            "Ghanbari M",
            "Gordon-Larsen P",
            "Huang W",
            "Kim YJ",
            "Tabara Y",
            "Wareham NJ",
            "Langenberg C",
            "Zeggini E",
            "Kuusisto J",
            "Laakso M",
            "Ingelsson E",
            "Abecasis G",
            "Chambers JC",
            "Kooner JS",
            "de Vries PS",
            "Morrison AC",
            "Hazelhurst S",
            "Ramsay M",
            "North KE",
            "Daviglus M",
            "Kraft P",
            "Martin NG",
            "Whitfield JB",
            "Abbas S",
            "Saleheen D",
            "Walters RG",
            "Holmes MV",
            "Black C",
            "Smith BH",
            "Baras A",
            "Justice AE",
            "Buring JE",
            "Ridker PM",
            "Chasman DI",
            "Kooperberg C",
            "Tamiya G",
            "Yamamoto M",
            "van Heel DA",
            "Trembath RC",
            "Wei WQ",
            "Jarvik GP",
            "Namjou B",
            "Hayes MG",
            "Ritchie MD",
            "Jousilahti P",
            "Salomaa V",
            "Hveem K",
            "\u00c5svold BO",
            "Kubo M",
            "Kamatani Y",
            "Okada Y",
            "Murakami Y",
            "Kim BJ",
            "Thorsteinsdottir U",
            "Stefansson K",
            "Zhang J",
            "Chen Y",
            "Ho YL",
            "Lynch JA",
            "Rader DJ",
            "Tsao PS",
            "Chang KM",
            "Cho K",
            "O'Donnell CJ",
            "Gaziano JM",
            "Wilson PWF",
            "Frayling TM",
            "Hirschhorn JN",
            "Kathiresan S",
            "Mohlke KL",
            "Sun YV",
            "Morris AP",
            "Boehnke M",
            "Brown CD",
            "Natarajan P",
            "Deloukas P",
            "Willer CJ",
            "Assimes TL",
            "Peloso GM"
        ],
        "doi": "10.1186/s13059-022-02837-1",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "422",
        "volume": "23",
        "issue": "1",
        "pages": "268",
        "pre": false,
        "pdate": "2022-12-28"
    },
    "10.15168/2284-4503-786": {
        "title": "The dynamic consent of the Cooperative Health Research in South Tyrol (CHRIS) study: broad aim within specific oversight and communication",
        "journal": "BioLaw Journal - Rivista di BioDiritto",
        "year": "2021",
        "abstract": "In biobanking and genomics research, data and samples are stored for long time and used in further studies, which may not be sufficiently specified or foreseen at the time of the initial consent. The dynamic consent of the CHRIS study integrates broad research aims, specific oversight and governance mechanisms, and continuous communication with participants, and allows nuanced choices to be changed over time. With this paper, we describe the CHRIS dynamic consent, and illustrate, by discussing data sharing and ongoing consent in the CHRIS study, how dynamic consent can actualize an informed consent model that is suitable for biobanking and genomic research.",
        "authors": [
            "Biasiotto R",
            "Pramstaller PP",
            "Mascalzoni D"
        ],
        "doi": "10.15168/2284-4503-786",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "421",
        "volume": "",
        "issue": "1S ",
        "pages": "277\u2013287",
        "pre": false,
        "pdate": "2021-01-01"
    },
    "10.5604/01.3001.0012.1364": {
        "title": "Zgoda dynamiczna w projekcie Chris Study [The Dynamic Consent in the Chris Study]",
        "journal": "Studia Iuridica",
        "year": "2018",
        "abstract": "The subject of the article is to describe the advantages of the new type of consent used for biobanking human biological samples which is dynamic consent. This consent will be described through the prism of the Italian study, CHRIS study. The biggest advantages of this consent is the possibility of its access to specific scientific research and broad information to the patient about the purpose of using his biological sample and data. The basic assumption is that the consent given by the donor should not be of a invariable nature (it is not written on stones), but it should be dynamic.",
        "authors": [
            "Mascalzoni D"
        ],
        "doi": "10.5604/01.3001.0012.1364",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "419",
        "volume": "73",
        "issue": "",
        "pages": "43 - 58",
        "pre": false,
        "pdate": "2018-01-01"
    },
    "10.1007/s12687-017-0328-2": {
        "title": "Legal issues in governing genetic biobanks: the Italian framework as a case study for the implications for citizen's health through public-private initiatives.",
        "journal": "Journal of community genetics",
        "year": "2018",
        "abstract": "This paper outlines some of the challenges faced by regulation of genetic biobanking, using case studies coming from the Italian legal system. The governance of genetic resources in the context of genetic biobanks in Italy is discussed, as an example of the stratification of different inputs and rules: EU law, national law, orders made by authorities and soft law, which need to be integrated with ethical principles, technological strategies and solutions. After providing an overview of the Italian legal regulation of genetic data processing, it considers the fate of genetic material and IP rights in the event of a biobank's insolvency. To this end, it analyses two case studies: a controversial bankruptcy case which occurred in Sardinia, one of the first examples of private and public partnership biobanks. Another case study considered is the Chris project: an example of partnership between a research institute in Bolzano and the South Tyrolean Health System. Both cases seem to point in the same direction, suggesting expediency of promoting and improving public-private partnerships to manage biological tissues and biotrust to conciliate patent law and public interest.",
        "authors": [
            "Piciocchi C",
            "Ducato R",
            "Martinelli L",
            "Perra S",
            "Tomasi M",
            "Zuddas C",
            "Mascalzoni D"
        ],
        "doi": "10.1007/s12687-017-0328-2",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "418",
        "volume": "9",
        "issue": "2",
        "pages": "177-190",
        "pre": false,
        "pdate": "2017-09-19"
    },
    "10.1186/s12910-016-0162-9": {
        "title": "Dynamic Consent: a potential solution to some of the challenges of modern biomedical research.",
        "journal": "BMC medical ethics",
        "year": "2017",
        "abstract": "**Background**<br> Innovations in technology have contributed to rapid changes in the way that modern biomedical research is carried out. Researchers are increasingly required to endorse adaptive and flexible approaches to accommodate these innovations and comply with ethical, legal and regulatory requirements. This paper explores how Dynamic Consent may provide solutions to address challenges encountered when researchers invite individuals to participate in research and follow them up over time in a continuously changing environment. <br>**Methods**<br> An interdisciplinary workshop jointly organised by the University of Oxford and the COST Action CHIP ME gathered clinicians, researchers, ethicists, lawyers, research participants and patient representatives to discuss experiences of using Dynamic Consent, and how such use may facilitate the conduct of specific research tasks. The data collected during the workshop were analysed using a content analysis approach. <br>**Results**<br> Dynamic Consent can provide practical, sustainable and future-proof solutions to challenges related to participant recruitment, the attainment of informed consent, participant retention and consent management, and may bring economic efficiencies. <br>**Conclusions**<br> Dynamic Consent offers opportunities for ongoing communication between researchers and research participants that can positively impact research. Dynamic Consent supports inter-sector, cross-border approaches and large scale data-sharing. Whilst it is relatively easy to set up and maintain, its implementation will require that researchers re-consider their relationship with research participants and adopt new procedures.",
        "authors": [
            "Budin-Lj\u00f8sne I",
            "Teare HJ",
            "Kaye J",
            "Beck S",
            "Bentzen HB",
            "Caenazzo L",
            "Collett C",
            "D'Abramo F",
            "Felzmann H",
            "Finlay T",
            "Javaid MK",
            "Jones E",
            "Kati\u0107 V",
            "Simpson A",
            "Mascalzoni D"
        ],
        "doi": "10.1186/s12910-016-0162-9",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "417",
        "volume": "18",
        "issue": "1",
        "pages": "4",
        "pre": false,
        "pdate": "2017-01-27"
    },
    "10.1186/1472-6823-14-9": {
        "title": "The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies.",
        "journal": "BMC endocrine disorders",
        "year": "2014",
        "abstract": "**Background**<br> Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies. <br>**Methods**<br> Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18-80\u00a0years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI\u2009\u2265\u200930\u00a0kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease. <br>**Results**<br> Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes. <br>**Conclusions**<br> Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics defining the metabolically healthy obese phenotype across ten cohort studies. There is considerable variability in the prevalence of healthy obesity across the different European populations studied, even when unified criteria were used to classify this phenotype.",
        "authors": [
            "van Vliet-Ostaptchouk JV",
            "Nuotio ML",
            "Slagter SN",
            "Doiron D",
            "Fischer K",
            "Foco L",
            "Gaye A",
            "G\u00f6gele M",
            "Heier M",
            "Hiekkalinna T",
            "Joensuu A",
            "Newby C",
            "Pang C",
            "Partinen E",
            "Reischl E",
            "Schwienbacher C",
            "Tammesoo ML",
            "Swertz MA",
            "Burton P",
            "Ferretti V",
            "Fortier I",
            "Giepmans L",
            "Harris JR",
            "Hillege HL",
            "Holmen J",
            "Jula A",
            "Kootstra-Ros JE",
            "Kval\u00f8y K",
            "Holmen TL",
            "M\u00e4nnist\u00f6 S",
            "Metspalu A",
            "Midthjell K",
            "Murtagh MJ",
            "Peters A",
            "Pramstaller PP",
            "Saaristo T",
            "Salomaa V",
            "Stolk RP",
            "Uusitupa M",
            "van der Harst P",
            "van der Klauw MM",
            "Waldenberger M",
            "Perola M",
            "Wolffenbuttel BH"
        ],
        "doi": "10.1186/1472-6823-14-9",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "416",
        "volume": "14",
        "issue": "",
        "pages": "9",
        "pre": false,
        "pdate": "2014-02-04"
    },
    "10.1111/ene.12244": {
        "title": "Association between restless legs syndrome and hypertension: a preliminary population-based study in South Tyrol, Italy.",
        "journal": "European journal of neurology",
        "year": "2014",
        "abstract": "**Background and purpose**<br> Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an irresistible urge to move the legs accompanied by paresthesia and/or dysesthesia that begins or worsens in the evening and night and that is partially or totally relieved by movement. Many studies have investigated the association between RLS and cardiovascular risk factors, particularly hypertension, leading to conflicting results. The aim of this study was to assess the association between RLS and hypertension considering also other cardiovascular risk factors that could act as confounders. <br>**Methods**<br> In all, 1709 participants of an on-going adult population-based study performed in South Tyrol, northern Italy, were enrolled. RLS was assessed through face-to-face interviews according to current International Restless Legs Syndrome Study Group diagnostic criteria. The presence of hypertension was self-reported and determined by questionnaires administered by trained study nurses. <br>**Results**<br> The association between RLS and hypertension was not significant after adjustment for age, sex, diabetes mellitus, history of myocardial infarction, raised blood lipids and body mass index (odds ratio 1.24, 95% CI 0.85-1.80, *P* = 0.271). <br>**Conclusion**<br> Despite the small sample size of this study, RLS and hypertension were not associated in our adult population after adjustment for possible confounding factors. The presence of other cardiovascular risk factors could play a role as a confounder of this association.",
        "authors": [
            "Giannini G",
            "Zanigni S",
            "Melotti R",
            "G\u00f6gele M",
            "Provini F",
            "Facheris MF",
            "Cortelli P",
            "Pramstaller PP"
        ],
        "doi": "10.1111/ene.12244",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "415",
        "volume": "21",
        "issue": "1",
        "pages": "72-8",
        "pre": false,
        "pdate": "2013-08-03"
    },
    "10.1111/ene.12462": {
        "title": "Association between restless legs syndrome and migraine: a population-based study.",
        "journal": "European journal of neurology",
        "year": "2014",
        "abstract": "**Background and purpose**<br> A higher prevalence of restless legs syndrome (RLS) in migraineurs has been reported in clinical samples and in two large-scale clinical trials performed on healthcare workers but general population-based studies on this topic are lacking. The aim of this study was to assess the association between migraine and RLS in an Italian rural adult population-based setting. <br>**Methods**<br> The presence of migraine and RLS was assessed via a computer-assisted personal interview and self-administered questionnaires according to current diagnostic criteria in 1567 participants of a preliminary phase of an adult population-based study performed in South Tyrol, Italy. <br>**Results**<br> Migraineurs had an increased risk of having RLS also after adjustment for confounding factors such as age, sex, major depression, anxiety and sleep quality (odds ratio 1.79; confidence interval 1.00-3.19; *P* = 0.049). This association was not modified by aura status and possible causes of secondary RLS. RLS was not significantly associated with tension-type headache. <br>**Conclusions**<br> Restless legs syndrome and migraine were associated in our rural adult population. This association could be explained by a possible shared pathogenic pathway which would implicate new management strategies of these two disorders.",
        "authors": [
            "Zanigni S",
            "Giannini G",
            "Melotti R",
            "Pattaro C",
            "Provini F",
            "Cevoli S",
            "Facheris MF",
            "Cortelli P",
            "Pramstaller PP"
        ],
        "doi": "10.1111/ene.12462",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "414",
        "volume": "21",
        "issue": "9",
        "pages": "1205-10",
        "pre": false,
        "pdate": "2014-05-21"
    },
    "10.1007/s12687-021-00536-1": {
        "title": "Return of research results (RoRR) to the healthy CHRIS cohort: designing a policy with the participants.",
        "journal": "Journal of community genetics",
        "year": "2021",
        "abstract": "Legal, financial and organizational challenges and the absence of coherent international guidelines and legal frameworks still discourage many genetic studies to share individual research results with their participants. Studies and institutions deciding to return genetic results will need to design their own study-specific return policy after due consideration of the ethical responsibilities. The Cooperative Health Research in South Tyrol (CHRIS) study, a healthy cohort study, did not foresee the return of individual genomic results during its baseline phase. However, as it was expected that the follow-up phase would generate an increasing amount of reliable genetic results, an update of the return of research results (RoRR) policy became necessary. To inform this revision, an empirical study using mixed methods was developed to investigate the views of CHRIS research participants (20), local general practitioners (3) and the local genetic counselling service (1). During the interviews, three different examples of potential genetic results with a very diverse potential impact on participants were presented: breast cancer, Parkinson disease and Huntington disease. The CHRIS participants also completed a short questionnaire, collecting personal information and asking for a self-evaluation of their knowledge about genetics. This study made it clear that research participants want to make autonomous decisions on the disclosure or non-disclosure of their results. While the motivations for participants' decisions were very diverse, we were able to identify several common criteria that had a strong influence on their choices. Providing information on these factors is crucial to enable participants to make truly informed decisions.",
        "authors": [
            "Staunton C",
            "K\u00f6sters M",
            "Pramstaller PP",
            "Mascalzoni D"
        ],
        "doi": "10.1007/s12687-021-00536-1",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "412",
        "volume": "12",
        "issue": "4",
        "pages": "577-592",
        "pre": false,
        "pdate": "2021-07-10"
    },
    "10.1038/s41431-021-00860-7": {
        "title": "Balancing scientific interests and the rights of participants in designing a recall by genotype study.",
        "journal": "European journal of human genetics",
        "year": "2021",
        "abstract": "Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants' views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.",
        "authors": [
            "Mascalzoni D",
            "Biasiotto R",
            "Borsche M",
            "Br\u00fcggemann N",
            "De Grandi A",
            "Goegele M",
            "Frygner-Holm S",
            "Klein C",
            "K\u00f6sters M",
            "Staunton C",
            "Pramstaller PP",
            "Krawczak M",
            "Hicks AA"
        ],
        "doi": "10.1038/s41431-021-00860-7",
        "source_study": [
            "CHRIS PAREGEN"
        ],
        "ar": "411",
        "volume": "29",
        "issue": "7",
        "pages": "1146-1157",
        "pre": false,
        "pdate": "2021-05-14"
    },
    "10.1038/s41467-022-32821-z": {
        "title": "Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.",
        "journal": "Nature communications",
        "year": "2022",
        "abstract": "The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.",
        "authors": [
            "Young WJ",
            "Lahrouchi N",
            "Isaacs A",
            "Duong T",
            "Foco L",
            "Ahmed F",
            "Brody JA",
            "Salman R",
            "Noordam R",
            "Benjamins JW",
            "Haessler J",
            "Lyytik\u00e4inen LP",
            "Repetto L",
            "Concas MP",
            "van den Berg ME",
            "Weiss S",
            "Baldassari AR",
            "Bartz TM",
            "Cook JP",
            "Evans DS",
            "Freudling R",
            "Hines O",
            "Isaksen JL",
            "Lin H",
            "Mei H",
            "Moscati A",
            "M\u00fcller-Nurasyid M",
            "Nursyifa C",
            "Qian Y",
            "Richmond A",
            "Roselli C",
            "Ryan KA",
            "Tarazona-Santos E",
            "Th\u00e9riault S",
            "van Duijvenboden S",
            "Warren HR",
            "Yao J",
            "Raza D",
            "Aeschbacher S",
            "Ahlberg G",
            "Alonso A",
            "Andreasen L",
            "Bis JC",
            "Boerwinkle E",
            "Campbell A",
            "Catamo E",
            "Cocca M",
            "Cutler MJ",
            "Darbar D",
            "De Grandi A",
            "De Luca A",
            "Ding J",
            "Ellervik C",
            "Ellinor PT",
            "Felix SB",
            "Froguel P",
            "Fuchsberger C",
            "G\u00f6gele M",
            "Graff C",
            "Graff M",
            "Guo X",
            "Hansen T",
            "Heckbert SR",
            "Huang PL",
            "Huikuri HV",
            "Hutri-K\u00e4h\u00f6nen N",
            "Ikram MA",
            "Jackson RD",
            "Junttila J",
            "Kavousi M",
            "Kors JA",
            "Leal TP",
            "Lemaitre RN",
            "Lin HJ",
            "Lind L",
            "Linneberg A",
            "Liu S",
            "MacFarlane PW",
            "Mangino M",
            "Meitinger T",
            "Mezzavilla M",
            "Mishra PP",
            "Mitchell RN",
            "Mononen N",
            "Montasser ME",
            "Morrison AC",
            "Nauck M",
            "Nauffal V",
            "Navarro P",
            "Nikus K",
            "Pare G",
            "Patton KK",
            "Pelliccione G",
            "Pittman A",
            "Porteous DJ",
            "Pramstaller PP",
            "Preuss MH",
            "Raitakari OT",
            "Reiner AP",
            "Ribeiro ALP",
            "Rice KM",
            "Risch L",
            "Schlessinger D",
            "Schotten U",
            "Schurmann C",
            "Shen X",
            "Shoemaker MB",
            "Sinagra G",
            "Sinner MF",
            "Soliman EZ",
            "Stoll M",
            "Strauch K",
            "Tarasov K",
            "Taylor KD",
            "Tinker A",
            "Trompet S",
            "Uitterlinden A",
            "V\u00f6lker U",
            "V\u00f6lzke H",
            "Waldenberger M",
            "Weng LC",
            "Whitsel EA",
            "Wilson JG",
            "Avery CL",
            "Conen D",
            "Correa A",
            "Cucca F",
            "D\u00f6rr M",
            "Gharib SA",
            "Girotto G",
            "Grarup N",
            "Hayward C",
            "Jamshidi Y",
            "J\u00e4rvelin MR",
            "Jukema JW",
            "K\u00e4\u00e4b S",
            "K\u00e4h\u00f6nen M",
            "Kanters JK",
            "Kooperberg C",
            "Lehtim\u00e4ki T",
            "Lima-Costa MF",
            "Liu Y",
            "Loos RJF",
            "Lubitz SA",
            "Mook-Kanamori DO",
            "Morris AP",
            "O'Connell JR",
            "Olesen MS",
            "Orini M",
            "Padmanabhan S",
            "Pattaro C",
            "Peters A",
            "Psaty BM",
            "Rotter JI",
            "Stricker B",
            "van der Harst P",
            "van Duijn CM",
            "Verweij N",
            "Wilson JF",
            "Arking DE",
            "Ramirez J",
            "Lambiase PD",
            "Sotoodehnia N",
            "Mifsud B",
            "Newton-Cheh C",
            "Munroe PB"
        ],
        "doi": "10.1038/s41467-022-32821-z",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "408",
        "volume": "13",
        "issue": "1",
        "pages": "5144",
        "pre": false,
        "pdate": "2022-09-02"
    },
    "10.1093/brain/awac464": {
        "title": "Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson's disease.",
        "journal": "Brain",
        "year": "2023",
        "abstract": "Biallelic mutations in *PINK1/PRKN* cause recessive Parkinson's disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA integrity and inflammation as disease modifiers in carriers of mutations in these genes. Mitochondrial DNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of *PINK1/PRKN* mutations, idiopathic Parkinson's disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected *PINK1/PRKN* monoallelic mutation carriers can be distinguished by heteroplasmic mitochondrial DNA variant load (area under the curve = 0.83, CI 0.74-0.93). Biallelic *PINK1/PRKN* mutation carriers harbour more heteroplasmic mitochondrial DNA variants in blood (P = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in induced pluripotent stem cell-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and post-mortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Last, the heteroplasmic mitochondrial DNA variant load correlated with IL6 levels in *PINK1/PRKN* mutation carriers (r = 0.57, *P* = 0.0074). *PINK1/PRKN* mutations predispose individuals to mitochondrial DNA variant accumulation in a dose- and disease-dependent manner.",
        "authors": [
            "Trinh J",
            "Hicks AA",
            "K\u00f6nig IR",
            "Delcambre S",
            "L\u00fcth T",
            "Schaake S",
            "Wasner K",
            "Ghelfi J",
            "Borsche M",
            "Vilari\u00f1o-G\u00fcell C",
            "Hentati F",
            "Germer EL",
            "Bauer P",
            "Takanashi M",
            "Kosti\u0107 V",
            "Lang AE",
            "Br\u00fcggemann N",
            "Pramstaller PP",
            "Pichler I",
            "Rajput A",
            "Hattori N",
            "Farrer MJ",
            "Lohmann K",
            "Weissensteiner H",
            "May P",
            "Klein C",
            "Gr\u00fcnewald A"
        ],
        "doi": "10.1093/brain/awac464",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "407",
        "volume": "146",
        "issue": "7",
        "pages": "2753-2765",
        "pre": false,
        "pdate": "2022-12-09"
    },
    "10.1038/s41598-023-42474-7": {
        "title": "Smoking and salivary microbiota: a cross-sectional analysis of an Italian alpine population.",
        "journal": "Scientific reports",
        "year": "2023",
        "abstract": "The oral microbiota plays an important role in the exogenous nitrate reduction pathway and is associated with heart and periodontal disease and cigarette smoking. We describe smoking-related changes in oral microbiota composition and resulting potential metabolic pathway changes that may explain smoking-related changes in disease risk. We analyzed health information and salivary microbiota composition among 1601 Cooperative Health Research in South Tyrol participants collected 2017-2018. Salivary microbiota taxa were assigned from amplicon sequences of the 16S-V4 rRNA and used to describe microbiota composition and predict metabolic pathways. Aerobic taxa relative abundance decreased with daily smoking intensity and increased with years since cessation, as did inferred nitrate reduction. Former smokers tended to be more similar to Never smokers than to Current smokers, especially those who had quit for longer than 5\u00a0years. Cigarette smoking has a consistent, generalizable association on oral microbiota composition and predicted metabolic pathways, some of which associate in a dose-dependent fashion. Smokers who quit for longer than 5\u00a0years tend to have salivary microbiota profiles comparable to never smokers.",
        "authors": [
            "Antonello G",
            "Blostein F",
            "Bhaumik D",
            "Davis E",
            "G\u00f6gele M",
            "Melotti R",
            "Pramstaller P",
            "Pattaro C",
            "Segata N",
            "Foxman B",
            "Fuchsberger C"
        ],
        "doi": "10.1038/s41598-023-42474-7",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "406",
        "volume": "13",
        "issue": "1",
        "pages": "18904",
        "pre": false,
        "pdate": "2023-11-03"
    },
    "10.1093/hmg/ddae062": {
        "title": "Impact of the inaccessible genome on genotype imputation and genome-wide association studies.",
        "journal": "Human molecular genetics",
        "year": "2024",
        "abstract": "Genotype imputation is widely used in genome-wide association studies (GWAS). However, both the genotyping chips and imputation reference panels are dependent on next-generation sequencing (NGS). Due to the nature of NGS, some regions of the genome are inaccessible to sequencing. To date, there has been no complete evaluation of these regions and their impact on the identification of associations in GWAS remains unclear. In this study, we systematically assess the extent to which variants in inaccessible regions are underrepresented on genotyping chips and imputation reference panels, in GWAS results and in variant databases. We also determine the proportion of genes located in inaccessible regions and compare the results across variant masks defined by the 1000 Genomes Project and the TOPMed program. Overall, fewer variants were observed in inaccessible regions in all categories analyzed. Depending on the mask used and normalized for region size, only 4%-17% of the genotyped variants are located in inaccessible regions and 52 to 581 genes were almost completely inaccessible. From the Cooperative Health Research in South Tyrol (CHRIS) study, we present a case study of an association located in an inaccessible region that is driven by genotyped variants and cannot be reproduced by imputation in GRCh37. We conclude that genotyping, NGS, genotype imputation and downstream analyses such as GWAS and fine mapping are systematically biased in inaccessible regions, due to missed variants and spurious associations. To help researchers assess gene and variant accessibility, we provide an online application ([https://gab.gm.eurac.edu](https://gab.gm.eurac.edu)).",
        "authors": [
            "K\u00f6nig E",
            "Mitchell JS",
            "Filosi M",
            "Fuchsberger C"
        ],
        "doi": "10.1093/hmg/ddae062",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "403",
        "volume": "33",
        "issue": "14",
        "pages": "1207-1214",
        "pre": false,
        "pdate": "2024-04-21"
    },
    "10.1093/chemse/bjae011": {
        "title": "Factors influencing olfactory function in an adult general population sample: the CHRIS study.",
        "journal": "Chemical senses",
        "year": "2024",
        "abstract": "The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most studies that aimed at identifying the variables that drive olfactory function in the population suffered from methodological weaknesses in study designs and participant selection, such as the inclusion of convenience sample or only of certain age groups, or recruitment biases. We aimed to overcome these issues by investigating the Cooperative Health Research in South Tyrol (CHRIS) cohort, a population-based cohort, by using a validated odor identification test. Specifically, we hypothesized that a series of medical, demographic and lifestyle variables is associated with odor identification abilities. In addition, our goal was to provide clinicians and researchers with normative values for the Sniffin' Sticks identification set, after exclusion of individuals with impaired nasal patency. We included 6,944 participants without acute nasal obstruction and assessed several biological, social, and medical parameters. A basic model determined that age, sex, years of education, and smoking status together explained roughly 13% of the total variance in the data. We further observed that variables related to medical (positive screening for cognitive impairment and for Parkinson's disease, history of skull fracture, stage 2 hypertension) and lifestyle (alcohol abstinence) conditions had a negative effect on odor identification scores. Finally, we provide clinicians with normative values for both versions of the Sniffin' Sticks odor identification test, i.e. with 16 items and with 12 items.",
        "authors": [
            "G\u00f6gele M",
            "Emmert D",
            "Fuchsberger C",
            "Frasnelli J"
        ],
        "doi": "10.1093/chemse/bjae011",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "401",
        "volume": "49",
        "issue": "",
        "pages": "",
        "pre": false,
        "pdate": "2024-03-07"
    },
    "10.1038/s43856-025-00856-0": {
        "title": "Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies.",
        "journal": "Communications medicine",
        "year": "2025",
        "abstract": "**Background**<br> The study of circulating blood proteins in population cohorts offers new avenues to explore lifestyle-related and genetic influences describing and shaping human health. <br>**Methods**<br> Utilizing high-throughput mass spectrometry, we quantified 148 highly abundant proteins, functioning in the innate and adaptive immune system, coagulation and nutrient transport in 3632 blood plasma, and 500 serum samples from the CHRIS and BASE-II cross-sectional population studies, respectively. Through multiple regression analyses, we aimed to identify the main factors influencing the circulating proteome at population level. <br>**Results**<br> Many demographic covariates and common medications affect the concentration of high-abundant plasma proteins, but the most significant changes are linked to the use of hormonal contraceptives (HCU). HCU particularly alters amongst others the levels of Angiotensinogen and Transcortin. We robustly replicated these findings in the BASE-II cohort. Furthermore, our results indicate that combined hormonal contraceptives with ethinylestradiol have a stronger effect compared to bioidentical estrogens. Our analysis detects no lasting impact of hormonal contraceptives on the plasma proteome. <br>**Conclusions**<br> HCU is the dominant factor reshaping the high-abundant circulating blood proteome in two population studies. Given the high prevalence of HCU among young women, it is essential to account for this treatment in human proteome studies to avoid misinterpreting its impact as sex- or age-related effects. Although we did not investigate the influence of HCU-induced proteomic changes on human health, our data suggest that future studies on this topic are warranted.",
        "authors": [
            "Dordevic N",
            "Dierks C",
            "Hantikainen E",
            "Farztdinov V",
            "Amari F",
            "Verri Hernandes V",
            "De Grandi A",
            "Domingues FS",
            "Shomroni O",
            "Textoris-Taube K",
            "Bahr V",
            "Schmid H",
            "Demuth I",
            "Kurth F",
            "M\u00fclleder M",
            "Pramstaller PP",
            "Rainer J",
            "Ralser M"
        ],
        "doi": "10.1038/s43856-025-00856-0",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "395",
        "volume": "5",
        "issue": "1",
        "pages": "131",
        "pre": false,
        "pdate": "2025-04-23"
    },
    "10.1002/mdc3.14201": {
        "title": "Archimedes Spiral Ratings: Determinants and Population-Based Limits of Normal.",
        "journal": "Movement disorders clinical practice",
        "year": "2024",
        "abstract": "**Background**<br> Tremor is commonly found among healthy humans or prevalently a symptom of neurological dysfunctions. However, the distinction between physiological and pathological tremor is dependent on the examiner's competence. Archimedes Spiral Rating (ASR) is a valid and reproducible semi-quantitative method to assess the severity of action tremor. <br>**Objectives**<br> (1) To assess the range and percentiles of ASR in a large sample seemingly free of tremor-related conditions or symptoms from the population-based CHRIS-study. (2) To analyze the influence of sex, age, and the drawing hand on ASR. (3) To define ASR limits of normal. (4) To supply exemplary Archimedes spiral drawings by each rating to favor consistent and proficient clinical evaluation. <br>**Methods**<br> Accurately investigated participants were randomly sampled over 14 sex-age strata. 2686 paired spirals drawn with both hands by 1343 participants were expertly assessed on a tremor rating scale from 0 to 9. <br>**Results**<br> ASR had a quadratic increase with age in both sexes, while it was relatively lower in the dominant compared to the non-dominant hand and in women compared to men. ASRs above sex-age specific 97.5th percentiles of 4 and 5, below and above 60\u2009years of age, respectively, were conceivably of non-physiological nature. <br>**Conclusions**<br> In a large population-based sample we show a steeper increase of action tremor by age as age progresses. Relatively higher ratings among the elderly, males and the non-dominant hands, appear compatible with ASR limits of \"normal\" across sex-age groups. The current operational evidence may support practitioners differentiating physiological and pathological hand tremor.",
        "authors": [
            "Hopfner F",
            "Tietz A",
            "D'Elia Y",
            "Pattaro C",
            "Becktepe JS",
            "G\u00f6gele M",
            "Barin L",
            "Pramstaller PP",
            "Kuhlenb\u00e4umer G",
            "Melotti R"
        ],
        "doi": "10.1002/mdc3.14201",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "391",
        "volume": "11",
        "issue": "10",
        "pages": "1257-1265",
        "pre": false,
        "pdate": "2024-09-05"
    },
    "10.1182/blood.2023022596": {
        "title": "Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.",
        "journal": "Blood",
        "year": "2024",
        "abstract": "Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program (n\u00a0=\u00a032\u2009572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n\u00a0=\u00a0131\u2009340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, 4 are driven by common variants of small effect with reported minor allele frequency (MAF) at least 10 percentage points higher in African populations. Three signals (*SERPINA1*, *ZFP36L2*, and *TLR10*) contain predicted deleterious missense variants. Two loci, *SOCS3* and *HPN*, each harbor 2 conditionally distinct, noncoding variants. The gene region encoding the fibrinogen protein chain subunits (*FGG*;*FGB*;*FGA*) contains 7 distinct signals, including 1 novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAF<sub>AFR</sub>\u00a0=\u00a00.180; MAF<sub>EUR</sub>\u00a0=\u00a00.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.",
        "authors": [
            "Huffman JE",
            "Nicholas J",
            "Hahn J",
            "Heath AS",
            "Raffield LM",
            "Yanek LR",
            "Brody JA",
            "Thibord F",
            "Almasy L",
            "Bartz TM",
            "Bielak LF",
            "Bowler RP",
            "Carrasquilla GD",
            "Chasman DI",
            "Chen MH",
            "Emmert DB",
            "Ghanbari M",
            "Haessler J",
            "Hottenga JJ",
            "Kleber ME",
            "Le NQ",
            "Lee J",
            "Lewis JP",
            "Li-Gao R",
            "Luan J",
            "Malmberg A",
            "Mangino M",
            "Marioni RE",
            "Martinez-Perez A",
            "Pankratz N",
            "Polasek O",
            "Richmond A",
            "Rodriguez BAT",
            "Rotter JI",
            "Steri M",
            "Suchon P",
            "Trompet S",
            "Weiss S",
            "Zare M",
            "Auer P",
            "Cho MH",
            "Christofidou P",
            "Davies G",
            "de Geus E",
            "Deleuze JF",
            "Delgado GE",
            "Ekunwe L",
            "Faraday N",
            "G\u00f6gele M",
            "Greinacher A",
            "Gao H",
            "Howard T",
            "Joshi PK",
            "Kilpel\u00e4inen TO",
            "Lahti J",
            "Linneberg A",
            "Naitza S",
            "Noordam R",
            "Pa\u00fcls-Verg\u00e9s F",
            "Rich SS",
            "Rosendaal FR",
            "Rudan I",
            "Ryan KA",
            "Souto JC",
            "van Rooij FJA",
            "Wang H",
            "Zhao W",
            "Becker LC",
            "Beswick A",
            "Brown MR",
            "Cade BE",
            "Campbell H",
            "Cho K",
            "Crapo JD",
            "Curran JE",
            "de Maat MPM",
            "Doyle M",
            "Elliott P",
            "Floyd JS",
            "Fuchsberger C",
            "Grarup N",
            "Guo X",
            "Harris SE",
            "Hou L",
            "Kolcic I",
            "Kooperberg C",
            "Menni C",
            "Nauck M",
            "O'Connell JR",
            "Orr\u00f9 V",
            "Psaty BM",
            "R\u00e4ikk\u00f6nen K",
            "Smith JA",
            "Soria JM",
            "Stott DJ",
            "van Hylckama Vlieg A",
            "Watkins H",
            "Willemsen G",
            "Wilson PWF",
            "Ben-Shlomo Y",
            "Blangero J",
            "Boomsma D",
            "Cox SR",
            "Dehghan A",
            "Eriksson JG",
            "Fiorillo E",
            "Fornage M",
            "Hansen T",
            "Hayward C",
            "Ikram MA",
            "Jukema JW",
            "Kardia SLR",
            "Lange LA",
            "M\u00e4rz W",
            "Mathias RA",
            "Mitchell BD",
            "Mook-Kanamori DO",
            "Morange PE",
            "Pedersen O",
            "Pramstaller PP",
            "Redline S",
            "Reiner A",
            "Ridker PM",
            "Silverman EK",
            "Spector TD",
            "V\u00f6lker U",
            "Wareham NJ",
            "Wilson JF",
            "Yao J",
            "Tr\u00e9gou\u00ebt DA",
            "Johnson AD",
            "Wolberg AS",
            "de Vries PS",
            "Sabater-Lleal M",
            "Morrison AC",
            "Smith NL"
        ],
        "doi": "10.1182/blood.2023022596",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "387",
        "volume": "144",
        "issue": "21",
        "pages": "2248-2265",
        "pre": false,
        "pdate": "2024-09-03"
    },
    "10.1038/s41598-024-52373-0": {
        "title": "Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number.",
        "journal": "Scientific reports",
        "year": "2024",
        "abstract": "Mitochondrial DNA copy number (mtDNA-CN) is a biomarker for mitochondrial dysfunction associated with several diseases. Previous genome-wide association studies (GWAS) have been performed to unravel underlying mechanisms of mtDNA-CN regulation. However, the identified gene regions explain only a small fraction of mtDNA-CN variability. Most of this data has been estimated from microarrays based on various pipelines. In the present study we aimed to (1) identify genetic loci for qPCR-measured mtDNA-CN from three studies (16,130 participants) using GWAS, (2) identify potential systematic differences between our qPCR derived mtDNA-CN measurements compared to the published microarray intensity-based estimates, and (3) disentangle the nuclear from mitochondrial regulation of the mtDNA-CN phenotype. We identified two genome-wide significant autosomal loci associated with qPCR-measured mtDNA-CN: at *HBS1L* (rs4895440, p\u2009=\u20093.39\u2009\u00d7\u200910<sup>-13</sup>) and *GSDMA* (rs56030650, p\u2009=\u20094.85\u2009\u00d7\u200910<sup>-08</sup>) genes. Moreover, 113/115 of the previously published SNPs identified by microarray-based analyses were significantly equivalent with our findings. In our study, the mitochondrial genome itself contributed only marginally to mtDNA-CN regulation as we only detected a single rare mitochondrial variant associated with mtDNA-CN. Furthermore, we incorporated mitochondrial haplogroups into our analyses to explore their potential impact on mtDNA-CN. However, our findings indicate that they do not exert any significant influence on our results.",
        "authors": [
            "Koller A",
            "Filosi M",
            "Weissensteiner H",
            "Fazzini F",
            "Gorski M",
            "Pattaro C",
            "Sch\u00f6nherr S",
            "Forer L",
            "Herold JM",
            "Stark KJ",
            "D\u00f6ttelmayer P",
            "Hicks AA",
            "Pramstaller PP",
            "W\u00fcrzner R",
            "Eckardt KU",
            "Heid IM",
            "Fuchsberger C",
            "Lamina C",
            "Kronenberg F"
        ],
        "doi": "10.1038/s41598-024-52373-0",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "372",
        "volume": "14",
        "issue": "1",
        "pages": "2083",
        "pre": false,
        "pdate": "2024-01-25"
    },
    "10.1038/s41598-024-75627-3": {
        "title": "Metabolite and protein associations with general health in the population-based CHRIS study.",
        "journal": "Scientific reports",
        "year": "2024",
        "abstract": "Identifying biomarkers able to discriminate individuals on different health trajectories is crucial to understand the molecular basis of age-related morbidity. We investigated multi-omics signatures of general health and organ-specific morbidity, as well as their interconnectivity. We examined cross-sectional metabolome and proteome data from 3,142 adults of the Cooperative Health Research in South Tyrol (CHRIS) study, an Alpine population study designed to investigate how human biology, environment, and lifestyle factors contribute to people's health over time. We had 174 metabolites and 148 proteins quantified from fasting serum and plasma samples. We used the Cumulative Illness Rating Scale (CIRS) Comorbidity Index (CMI), which considers morbidity in 14 organ systems, to assess health status (any morbidity vs. healthy). Omics-signatures for health status were identified using random forest (RF) classifiers. Linear regression models were fitted to assess directionality of omics markers and health status associations, as well as to identify omics markers related to organ-specific morbidity. Next to age, we identified 21 metabolites and 10 proteins as relevant predictors of health status and results confirmed associations for serotonin and glutamate to be age-independent. Considering organ-specific morbidity, several metabolites and proteins were jointly related to endocrine, cardiovascular, and renal morbidity. To conclude, circulating serotonin was identified as a potential novel predictor for overall morbidity.",
        "authors": [
            "Hantikainen E",
            "Weichenberger CX",
            "Dordevic N",
            "Verri Hernandes V",
            "Foco L",
            "G\u00f6gele M",
            "Melotti R",
            "Pattaro C",
            "Ralser M",
            "Amari F",
            "Farztdinov V",
            "M\u00fclleder M",
            "Pramstaller PP",
            "Rainer J",
            "Domingues FS"
        ],
        "doi": "10.1038/s41598-024-75627-3",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "368",
        "volume": "14",
        "issue": "1",
        "pages": "26635",
        "pre": false,
        "pdate": "2024-11-05"
    },
    "10.1371/journal.pone.0323057": {
        "title": "Systematic mediation and interaction analyses of kidney function genetic loci in a general population study.",
        "journal": "PloS one",
        "year": "2025",
        "abstract": "Chronic kidney disease (CKD) is a complex disease affecting >10% of the global population, with large between- and within-continent variability reflecting major environmental determinants. To identify molecular targets for treatment and prevention, genome-wide association study meta-analyses (GWAMAs) of CKD-defining traits have identified hundreds of genetic loci in aggregated population samples. However, while GWAMAs estimate the average allelic effect across studies, single population studies may be relevant to unravel specific mechanisms. To assess whether a study sample from a specific population could extend existing knowledge on kidney function genetics, we selected 147 kidney function relevant loci identified by a large GWAMA, assessing their association with the glomerular filtration rate estimated from serum creatinine (eGFRcrea) in 10,146 participants to the Cooperative Health Research In South Tyrol (CHRIS) study, conducted in an Alpine region where thyroid dysfunction is common. We identified associations with single nucleotide polymorphisms (SNPs) at 11 loci, showing up-to-5.4 times larger effect sizes than in the corresponding GWAMA, not explainable by allele frequency differences. Systematic mediation analysis across 70 quantitative traits identified serum magnesium and the activated partial thromboplastin time as partial mediators of the eGFRcrea associations at *SHROOM3* and *SLC34A1*, respectively. Given that free triiodothyronine and thyroxine acted as effect modifiers across all loci, we conducted SNP-by-thyroid stimulating hormone (TSH) interaction analyses, identifying significant interactions at *STC1:* SNPs had larger effects on eGFRcrea at higher TSH levels, possibly reflecting stanniocalcin-1 autocrine and paracrine role. Individual population studies can help characterize genetic associations. The interplay between phenotypes at *SHROOM3* and *SLC34A1* and the role of thyroid function as a genetic effect modifier warrant further investigations.",
        "authors": [
            "Ghasemi-Semeskandeh D",
            "Emmert D",
            "K\u00f6nig E",
            "Foco L",
            "G\u00f6gele M",
            "Sarhan MS",
            "Barin L",
            "Fujii R",
            "Fuchsberger C",
            "Peters DJM",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1371/journal.pone.0323057",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "367",
        "volume": "20",
        "issue": "6",
        "pages": "e0323057",
        "pre": false,
        "pdate": "2025-06-24"
    },
    "10.1136/bmjopen-2023-072650": {
        "title": "Trends and symptoms of SARS-CoV-2 infection: a longitudinal study on an Alpine population representative sample.",
        "journal": "BMJ open",
        "year": "2023",
        "abstract": "**Objectives**<br> The continuous monitoring of SARS-CoV-2 infection waves and the emergence of novel pathogens pose a challenge for effective public health surveillance strategies based on diagnostics. Longitudinal population representative studies on incident events and symptoms of SARS-CoV-2 infection are scarce. We aimed at describing the evolution of the COVID-19 pandemic during 2020 and 2021 through regular monitoring of self-reported symptoms in an Alpine community sample. <br>**Design**<br> To this purpose, we designed a longitudinal population representative study, the Cooperative Health Research in South Tyrol COVID-19 study. <br>**Participants and outcome measures**<br> A sample of 845 participants was retrospectively investigated for active and past infections with swab and blood tests, by August 2020, allowing adjusted cumulative incidence estimation. Of them, 700 participants without previous infection or vaccination were followed up monthly until July 2021 for first-time infection and symptom self-reporting: COVID-19 anamnesis, social contacts, lifestyle and sociodemographic data were assessed remotely through digital questionnaires. Temporal symptom trajectories and infection rates were modelled through longitudinal clustering and dynamic correlation analysis. Negative binomial regression and random forest analysis assessed the relative importance of symptoms. <br>**Results**<br> At baseline, the cumulative incidence of SARS-CoV-2 infection was 1.10% (95% CI 0.51%, 2.10%). Symptom trajectories mimicked both self-reported and confirmed cases of incident infections. Cluster analysis identified two groups of high-frequency and low-frequency symptoms. Symptoms like fever and loss of smell fell in the low-frequency cluster. Symptoms most discriminative of test positivity (loss of smell, fatigue and joint-muscle aches) confirmed prior evidence. <br>**Conclusions**<br> Regular symptom tracking from population representative samples is an effective screening tool auxiliary to laboratory diagnostics for novel pathogens at critical times, as manifested in this study of COVID-19 patterns. Integrated surveillance systems might benefit from more direct involvement of citizens' active symptom tracking.",
        "authors": [
            "Barbieri G",
            "Pizzato M",
            "G\u00f6gele M",
            "Giardiello D",
            "Weichenberger CX",
            "Foco L",
            "Bottigliengo D",
            "Bertelli C",
            "Barin L",
            "Lundin R",
            "Pramstaller PP",
            "Pattaro C",
            "Melotti R"
        ],
        "doi": "10.1136/bmjopen-2023-072650",
        "source_study": [
            "CHRIS COVID-19"
        ],
        "ar": "357",
        "volume": "13",
        "issue": "6",
        "pages": "e072650",
        "pre": false,
        "pdate": "2023-06-09"
    },
    "10.1371/journal.pone.0280600": {
        "title": "Structural equation modeling (SEM) of kidney function markers and longitudinal CVD risk assessment.",
        "journal": "PloS one",
        "year": "2023",
        "abstract": "Lower kidney function is known to enhance cardiovascular disease (CVD) risk. It is unclear which estimated glomerular filtration rate (eGFR) equation best predict an increased CVD risk and if prediction can be improved by integration of multiple kidney function markers. We performed structural equation modeling (SEM) of kidney markers and compared the performance of the resulting pooled indexes with established eGFR equations to predict CVD risk in a 10-year longitudinal population-based design. We split the study sample into a set of participants with only baseline data (n = 647; model-building set) and a set with longitudinal data (n = 670; longitudinal set). In the model-building set, we fitted five SEM models based on serum creatinine or creatinine-based eGFR (eGFRcre), cystatin C or cystatin-based eGFR (eGFRcys), uric acid (UA), and blood urea nitrogen (BUN). In the longitudinal set, 10-year incident CVD risk was defined as a Framingham risk score (FRS)>5% and a pooled cohort equation (PCE)>5%. Predictive performances of the different kidney function indexes were compared using the C-statistic and the DeLong test. In the longitudinal set, a SEM-based estimate of latent kidney function based on eGFRcre, eGFRcys, UA, and BUN showed better prediction performance for both FRS>5% (C-statistic: 0.70; 95% CI: 0.65-0.74) and PCE>5% (C-statistic: 0.75; 95%CI: 0.71-0.79) than other SEM models and different eGFR formulas (DeLong test *p*-values<3.21\u00d710<sup>-6</sup> for FRS>5% and <1.49\u00d710<sup>-9</sup> for PCE>5%, respectively). However, the new derived marker could not outperform eGFRcys (DeLong test *p*-values = 0.88 for FRS>5% and 0.20 for PCE>5%, respectively). SEM is a promising approach to identify latent kidney function signatures. However, for incident CVD risk prediction, eGFRcys could still be preferrable given its simpler derivation.",
        "authors": [
            "Fujii R",
            "Melotti R",
            "G\u00f6gele M",
            "Barin L",
            "Ghasemi-Semeskandeh D",
            "Barbieri G",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1371/journal.pone.0280600",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "344",
        "volume": "18",
        "issue": "4",
        "pages": "e0280600",
        "pre": false,
        "pdate": "2023-04-20"
    },
    "10.1161/ATVBAHA.122.318213": {
        "title": "Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.",
        "journal": "Arteriosclerosis, thrombosis, and vascular biology",
        "year": "2023",
        "abstract": "**Background**<br> Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total. <br>**Methods**<br> Study participants were of European and African ancestries, and genotype data were imputed to TOPMed, a dense multiancestry reference panel. Each of the 10 studies conducted a genome-wide association studies for each phenotype and summary results were meta-analyzed, stratified by ancestry. Analysis of antithrombin included 25\u2009243 European ancestry and 2688 African ancestry participants, PC analysis included 16\u2009597 European ancestry and 2688 African ancestry participants, PSF and PST analysis included 4113 and 6409 European ancestry participants. We also conducted transcriptome-wide association analyses and multiphenotype analysis to discover additional associations. Novel genome-wide association studies and transcriptome-wide association analyses findings were validated by in vitro functional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes. <br>**Results**<br> Genome-wide association studies meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (*GCKR*, *BAZ1B*, and *HP-TXNL4B*) and 1 with PS levels (*ORM1-ORM2*). Transcriptome-wide association analyses identified 3 newly associated genes: 1 with antithrombin level (*FCGRT*), 1 with PC (*GOLM2*), and 1 with PS (*MYL7*). In addition, we replicated 7 independent loci reported in previous studies. Functional experiments provided evidence for the involvement of *GCKR*, *SNX17*, and *HP* genes in antithrombin regulation. <br>**Conclusions**<br> The use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels.",
        "authors": [
            "Ji Y",
            "Temprano-Sagrera G",
            "Holle LA",
            "Bebo A",
            "Brody JA",
            "Le NQ",
            "Kangro K",
            "Brown MR",
            "Martinez-Perez A",
            "Sitlani CM",
            "Suchon P",
            "Kleber ME",
            "Emmert DB",
            "Bilge Ozel A",
            "Dobson DA",
            "Tang W",
            "Llobet D",
            "Tracy RP",
            "Deleuze JF",
            "Delgado GE",
            "G\u00f6gele M",
            "Wiggins KL",
            "Souto JC",
            "Pankow JS",
            "Taylor KD",
            "Tr\u00e9gou\u00ebt DA",
            "Moissl AP",
            "Fuchsberger C",
            "Rosendaal FR",
            "Morrison AC",
            "Soria JM",
            "Cushman M",
            "Morange PE",
            "M\u00e4rz W",
            "Hicks AA",
            "Desch KC",
            "Johnson AD",
            "de Vries PS",
            "Wolberg AS",
            "Smith NL",
            "Sabater-Lleal M"
        ],
        "doi": "10.1161/ATVBAHA.122.318213",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "342",
        "volume": "43",
        "issue": "7",
        "pages": "e254-e269",
        "pre": false,
        "pdate": "2023-05-02"
    },
    "10.1038/s41431-022-01277-6": {
        "title": "Participant perspective on the recall-by-genotype research approach: a mixed-method embedded study with participants of the CHRIS study.",
        "journal": "European journal of human genetics",
        "year": "2023",
        "abstract": "Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner that addresses the potential ethical and social issues. As part of an RbG pilot on the penetrance of Parkinson's disease variants, we conducted an empirical mixed-method study with 51 participants of the Cooperative Health Research in South Tyrol (CHRIS) study to understand participant views on RbG research approach. Participants were disclosed the disease under investigation but not the individual variant carrier status. Results showed that participants filtered the information received through personal experience and enacted mechanisms to address the concerns raised by invitation by resorting to personal resources and the support provided by experts. While the non-disclosure of the Parkin variant carrier status was deemed acceptable, disclosing the disease under study was important for participants. Participant preferences for disclosure of the disease under investigation and the carrier status varied according to how the knowledge of individual carrier status was perceived to impact the participant's life. This study provided insights into participant response to the RbG research approach, which are relevant for RbG policy development. A suitable communication strategy and granular options addressing preferences for invitation in the original informed consent are critical for an ethically informed RbG policy.",
        "authors": [
            "Biasiotto R",
            "K\u00f6sters M",
            "Tschigg K",
            "Pramstaller PP",
            "Br\u00fcggemann N",
            "Borsche M",
            "Klein C",
            "Hicks AA",
            "Mascalzoni D"
        ],
        "doi": "10.1038/s41431-022-01277-6",
        "source_study": [
            "CHRIS PAREGEN",
            "CHRIS PAREGEN2"
        ],
        "ar": "332",
        "volume": "31",
        "issue": "11",
        "pages": "1218-1227",
        "pre": false,
        "pdate": "2023-01-05"
    },
    "10.1186/s12874-023-01930-8": {
        "title": "Cluster analysis of angiotensin biomarkers to identify antihypertensive drug treatment in population studies.",
        "journal": "BMC medical research methodology",
        "year": "2023",
        "abstract": "**Background**<br> The recent progress in molecular biology generates an increasing interest in investigating molecular biomarkers as markers of response to treatments. The present work is motivated by a study, where the objective was to explore the potential of the molecular biomarkers of renin-angiotensin-aldosterone system (RAAS) to identify the undertaken antihypertensive treatments in the general population. Population-based studies offer an opportunity to assess the effectiveness of treatments in real-world scenarios. However, lack of quality documentation, especially when electronic health record linkage is unavailable, leads to inaccurate reporting and classification bias. <br>**Method**<br> We present a machine learning clustering technique to determine the potential of measured RAAS biomarkers for the identification of undertaken treatments in the general population. The biomarkers were simultaneously determined through a novel mass-spectrometry analysis in 800 participants of the Cooperative Health Research In South Tyrol (CHRIS) study with documented antihypertensive treatments. We assessed the agreement, sensitivity and specificity of the resulting clusters against known treatment types. Through the lasso penalized regression, we identified clinical characteristics associated with the biomarkers, accounting for the effects of cluster and treatment classifications. <br>**Results**<br> We identified three well-separated clusters: cluster 1 (n\u2009=\u2009444) preferentially including individuals not receiving RAAS-targeting drugs; cluster 2 (n\u2009=\u2009235) identifying angiotensin type 1 receptor blockers (ARB) users (weighted kappa \u03ba<sub>w</sub>)\u2009=\u200974%; sensitivity\u2009=\u200973%; specificity\u2009=\u200983%); and cluster 3 (n\u2009=\u2009121) well discriminating angiotensin-converting enzyme inhibitors (ACEi) users (\u03ba<sub>w</sub>\u2009=\u200981%; sensitivity\u2009=\u200955%; specificity\u2009=\u200990%). Individuals in clusters 2 and 3 had higher frequency of diabetes as well as higher fasting glucose and BMI levels. Age, sex and kidney function were strong predictors of the RAAS biomarkers independently of the cluster structure. <br>**Conclusions**<br> Unsupervised clustering of angiotensin-based biomarkers is a viable technique to identify individuals on specific antihypertensive treatments, pointing to a potential application of the biomarkers as useful clinical diagnostic tools even outside of a controlled clinical setting.",
        "authors": [
            "Arisido MW",
            "Foco L",
            "Shoemaker R",
            "Melotti R",
            "Delles C",
            "G\u00f6gele M",
            "Barolo S",
            "Baron S",
            "Azizi M",
            "Dominiczak AF",
            "Zennaro MC",
            "P Pramstaller P",
            "Poglitsch M",
            "Pattaro C"
        ],
        "doi": "10.1186/s12874-023-01930-8",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "330",
        "volume": "23",
        "issue": "1",
        "pages": "131",
        "pre": false,
        "pdate": "2023-05-28"
    },
    "10.3390/metabo12070604": {
        "title": "Whole Exome Sequencing Enhanced Imputation Identifies 85 Metabolite Associations in the Alpine CHRIS Cohort.",
        "journal": "Metabolites",
        "year": "2022",
        "abstract": "Metabolites are intermediates or end products of biochemical processes involved in both health and disease. Here, we take advantage of the well-characterized Cooperative Health Research in South Tyrol (CHRIS) study to perform an exome-wide association study (ExWAS) on absolute concentrations of 175 metabolites in 3294 individuals. To increase power, we imputed the identified variants into an additional 2211 genotyped individuals of CHRIS. In the resulting dataset of 5505 individuals, we identified 85 single-variant genetic associations, of which 39 have not been reported previously. Fifteen associations emerged at ten variants with >5-fold enrichment in CHRIS compared to non-Finnish Europeans reported in the gnomAD database. For example, the CHRIS-enriched *ETFDH* stop gain variant p.Trp286Ter (rs1235904433-hexanoylcarnitine) and the *MCCC2* stop lost variant p.Ter564GlnextTer3 (rs751970792-carnitine) have been found in patients with glutaric acidemia type II and 3-methylcrotonylglycinuria, respectively, but the loci have not been associated with the respective metabolites in a genome-wide association study (GWAS) previously. We further identified three gene-trait associations, where multiple rare variants contribute to the signal. These results not only provide further evidence for previously described associations, but also describe novel genes and mechanisms for diseases and disease-related traits.",
        "authors": [
            "K\u00f6nig E",
            "Rainer J",
            "Hernandes VV",
            "Paglia G",
            "Del Greco M F",
            "Bottigliengo D",
            "Yin X",
            "Chan LS",
            "Teumer A",
            "Pramstaller PP",
            "Locke AE",
            "Fuchsberger C"
        ],
        "doi": "10.3390/metabo12070604",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "328",
        "volume": "12",
        "issue": "7",
        "pages": "",
        "pre": false,
        "pdate": "2022-07-28"
    },
    "10.1007/s40620-022-01409-7": {
        "title": "Association of dietary proteins with serum creatinine and estimated glomerular filtration rate in a general population sample: the CHRIS study.",
        "journal": "Journal of nephrology",
        "year": "2023",
        "abstract": "**Background**<br> Diet is known to affect kidney function. However, population-based studies provide contrasting evidence, resulting in a poor understanding of the effect of proteins from specific foods on kidney health. <br>**Methods**<br> We analyzed the effect of total daily protein intake (TDPI) and source-specific daily\u00a0protein intake (DPI) on fasting serum\u00a0creatinine (SCr) and estimated glomerular filtration rate (eGFR) in the Cooperative Health Research In South Tyrol (CHRIS) cross-sectional study (n\u2009=\u20095889), using the GA<sup>2</sup>LEN food frequency questionnaire for TDPI and DPI estimation. We fitted multivariable adjusted mixed models of SCr and eGFR on TDPI and DPI quartiles (Q1-Q4) in the overall sample, and after removing individuals with known hypertension, diabetes or chronic kidney disease (CKD). <br>**Results**<br> Higher TDPI as well as DPI from overall animal sources, fish, and poultry, were associated with higher SCr (trend test p, *p*<sub>trend</sub>\u2009<\u20090.01), with larger effect after excluding individuals with known hypertension, diabetes or CKD. The\u00a0eGFR was lower at higher TDPI (Q4 vs Q1: -\u20091.6\u00a0ml/min/1.73\u00a0m<sup>2</sup>; 95% CI -\u20092.5, -\u20090.7; *p*<sub>trend</sub>\u2009=\u20093e-4) and DPI from fish (Q4 vs Q1: -\u20092.1\u00a0ml/min/1.73\u00a0m<sup>2</sup>; 95% CI -\u20092.9, -\u20091.20; *p*<sub>trend</sub>\u2009=\u20094.3e-6), overall animal source (Q4 vs Q1: -\u20091.6\u00a0ml/min/1.73\u00a0m<sup>2</sup>; 95% CI -2.5, -\u20090.8), processed meat (Q4 vs Q1: -\u20091.4\u00a0ml/min/1.73\u00a0m<sup>2</sup>; *p*<sub>trend</sub>\u2009=\u20090.027), red meat, offal and processed meat (Q4 vs Q1: -\u20091.4\u00a0ml/min/1.73\u00a0m<sup>2</sup>; *p*<sub>trend</sub>\u2009=\u20090.015) and poultry (Q4 vs Q1: -\u20090.9\u00a0ml/min/1.73\u00a0m<sup>2</sup>; *p*<sub>trend</sub>\u2009=\u20090.015). <br>**Conclusions**<br> TDPI and DPI from specific animal sources were positively associated with SCr and negatively associated with eGFR. Lacking an alternative marker of kidney function, confounding involving muscle mass metabolism cannot be fully excluded.",
        "authors": [
            "Vukovic V",
            "Hantikainen E",
            "Raftopoulou A",
            "G\u00f6gele M",
            "Rainer J",
            "Domingues FS",
            "Pramstaller PP",
            "Garcia-Larsen V",
            "Pattaro C"
        ],
        "doi": "10.1007/s40620-022-01409-7",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "327",
        "volume": "36",
        "issue": "1",
        "pages": "103-114",
        "pre": false,
        "pdate": "2022-08-06"
    },
    "10.1038/s41531-023-00499-9": {
        "title": "Molecular phenotypes of mitochondrial dysfunction in clinically non-manifesting heterozygous PRKN variant carriers.",
        "journal": "NPJ Parkinson's disease",
        "year": "2023",
        "abstract": "Homozygous or compound heterozygous (biallelic) variants in *PRKN* are causal for PD with highly penetrant symptom expression, while the much more common heterozygous variants may predispose to PD with highly reduced penetrance, through altered mitochondrial function. In the presence of pathogenic heterozygous variants, it is therefore important to test for mitochondrial alteration in cells derived from variant carriers to establish potential presymptomatic molecular markers. We generated lymphoblasts (LCLs) and human induced pluripotent stem cell (hiPSC)-derived neurons from non-manifesting heterozygous *PRKN* variant carriers and tested them for mitochondrial functionality. In LCLs, we detected hyperactive mitochondrial respiration, and, although milder compared to a biallelic *PRKN*-PD patient, hiPSC-derived neurons of non-manifesting heterozygous variant carriers also displayed several phenotypes of altered mitochondrial function. Overall, we identified molecular phenotypes that might be used to monitor heterozygous *PRKN* variant carriers during the prodromal phase. Such markers might also be useful to identify individuals at greater risk of eventual disease development and for testing potential mitochondrial function-based neuroprotective therapies before neurodegeneration advances.",
        "authors": [
            "Castelo Rueda MP",
            "Zanon A",
            "Gilmozzi V",
            "Lavdas AA",
            "Raftopoulou A",
            "Delcambre S",
            "Del Greco M F",
            "Klein C",
            "Gr\u00fcnewald A",
            "Pramstaller PP",
            "Hicks AA",
            "Pichler I"
        ],
        "doi": "10.1038/s41531-023-00499-9",
        "source_study": [
            "CHRIS PAREGEN",
            "CHRIS PAREGEN2",
            "CHRIS baseline"
        ],
        "ar": "309",
        "volume": "9",
        "issue": "1",
        "pages": "65",
        "pre": false,
        "pdate": "2023-04-19"
    },
    "10.1038/s41467-023-36997-w": {
        "title": "Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.",
        "journal": "Nature communications",
        "year": "2023",
        "abstract": "The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N\u2009=\u2009118,780) and 11 for the frontal QRS-T angle (N\u2009=\u2009159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration.\u00a0Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism\u00a0and\u00a0genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle\u00a0and\u00a0their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.",
        "authors": [
            "Young WJ",
            "Haessler J",
            "Benjamins JW",
            "Repetto L",
            "Yao J",
            "Isaacs A",
            "Harper AR",
            "Ramirez J",
            "Garnier S",
            "van Duijvenboden S",
            "Baldassari AR",
            "Concas MP",
            "Duong T",
            "Foco L",
            "Isaksen JL",
            "Mei H",
            "Noordam R",
            "Nursyifa C",
            "Richmond A",
            "Santolalla ML",
            "Sitlani CM",
            "Soroush N",
            "Th\u00e9riault S",
            "Trompet S",
            "Aeschbacher S",
            "Ahmadizar F",
            "Alonso A",
            "Brody JA",
            "Campbell A",
            "Correa A",
            "Darbar D",
            "De Luca A",
            "Deleuze JF",
            "Ellervik C",
            "Fuchsberger C",
            "Goel A",
            "Grace C",
            "Guo X",
            "Hansen T",
            "Heckbert SR",
            "Jackson RD",
            "Kors JA",
            "Lima-Costa MF",
            "Linneberg A",
            "Macfarlane PW",
            "Morrison AC",
            "Navarro P",
            "Porteous DJ",
            "Pramstaller PP",
            "Reiner AP",
            "Risch L",
            "Schotten U",
            "Shen X",
            "Sinagra G",
            "Soliman EZ",
            "Stoll M",
            "Tarazona-Santos E",
            "Tinker A",
            "Trajanoska K",
            "Villard E",
            "Warren HR",
            "Whitsel EA",
            "Wiggins KL",
            "Arking DE",
            "Avery CL",
            "Conen D",
            "Girotto G",
            "Grarup N",
            "Hayward C",
            "Jukema JW",
            "Mook-Kanamori DO",
            "Olesen MS",
            "Padmanabhan S",
            "Psaty BM",
            "Pattaro C",
            "Ribeiro ALP",
            "Rotter JI",
            "Stricker BH",
            "van der Harst P",
            "van Duijn CM",
            "Verweij N",
            "Wilson JG",
            "Orini M",
            "Charron P",
            "Watkins H",
            "Kooperberg C",
            "Lin HJ",
            "Wilson JF",
            "Kanters JK",
            "Sotoodehnia N",
            "Mifsud B",
            "Lambiase PD",
            "Tereshchenko LG",
            "Munroe PB"
        ],
        "doi": "10.1038/s41467-023-36997-w",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "308",
        "volume": "14",
        "issue": "1",
        "pages": "1411",
        "pre": false,
        "pdate": "2023-03-16"
    },
    "10.1016/j.jad.2022.08.015": {
        "title": "Pain sensitivity is modulated by affective temperament: Results from the population-based CHRIS Affective Disorder (CHRIS-AD) study.",
        "journal": "Journal of affective disorders",
        "year": "2022",
        "abstract": "**Background**<br> Nociceptive pain modulation is related to psychological and psychiatric conditions. Evidence from clinical studies backs innate temperaments as potential precursors of mood symptoms and disorders, and pain sensitivity. Our study examines the modulation effect of affective temperaments on pain sensitivity in a general population adult sample, accounting for possible intervening mood symptoms, lifetime anxiety and depression, and pain treatments. <br>**Methods**<br> The sample is part of the CHRIS-AD study, Italy. Primary outcomes were the pain sensitivity questionnaire PSQ-total intensity score and the experimental pressure pain threshold (PPT). Affective temperaments were evaluated with the TEMPS-M. Lifetime depression, anxiety, current mood disorders, and treatments were self-reported via rating-scales. Directed acyclic graphs theory guided linear and mixed linear regression model analyses. <br>**Results**<br> Among 3804 participants (aged 18-65; response rate 78.4\u00a0%, females 53.3\u00a0%, mean age 38.4\u00a0years) for any given temperament, both the PSQ-total and the PPT were associated with temperament. The TEMPS-M four cyclothymic-related temperaments aligned on the pain-sensitive pole and the hyperthymic on the pain-resilient pole. The inclusion of current or lifetime mood symptoms, or pain drug use, as possible intervening pathways only partly diluted these associations, with stronger evidence for an effect of trait anxiety. <br>**Limitations**<br> The main limitations were the lack of experimental measures of suprathreshold pain intensity perception, and detailed information on affective disorders in the study population. <br>**Conclusions**<br> These findings support the hypothesis of a biological dichotomous diathesis of affective temperaments towards pain sensitivity; hyperthymic suggesting protection, whereas cyclothymic suggesting predisposition.",
        "authors": [
            "Favaretto E",
            "G\u00f6gele M",
            "Bedani F",
            "Hicks AA",
            "Erfurth A",
            "Perugi G",
            "Pramstaller PP",
            "Melotti R"
        ],
        "doi": "10.1016/j.jad.2022.08.015",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "307",
        "volume": "316",
        "issue": "",
        "pages": "209-216",
        "pre": false,
        "pdate": "2022-08-12"
    },
    "10.1080/20477724.2021.1978225": {
        "title": "Prospective epidemiological, molecular, and genetic characterization of a novel coronavirus disease in the Val Venosta/Vinschgau: the CHRIS COVID-19 study protocol.",
        "journal": "Pathogens and global health",
        "year": "2022",
        "abstract": "The COVID-19 pandemic has been threatening the healthcare and socioeconomic systems of entire nations. While population-based surveys to assess the distribution of SARS-CoV-2 infection have become a priority, pre-existing longitudinal studies are ideally suited to assess the determinants of COVID-19 onset and severity.The Cooperative Health Research In South Tyrol (CHRIS) study completed the baseline recruitment of 13,393 adults from the Venosta/Vinschgau rural district in 2018, collecting extensive phenotypic and biomarker data, metabolomic data, densely imputed genotype and whole-exome sequencing data.Based on CHRIS, we designed a prospective study, called CHRIS COVID-19, aimed at: 1) estimating the incidence of SARS-CoV-2 infections; 2) screening for and investigating the determinants of incident infection among CHRIS participants and their household members; 3) monitoring the immune response of infected participants prospectively.An online screening questionnaire was sent to all CHRIS participants and their household members. A random sample of 1450 participants representative of the district population was invited to assess active (nasopharyngeal swab) or past (serum antibody test) infections. We prospectively invited for complete SARS-CoV-2 testing all questionnaire completers gauged as possible cases of past infection and their household members. In positive tested individuals, antibody response is monitored quarterly for one year. Untested and negative participants receive the screening questionnaire every four weeks until gauged as possible incident cases or till the study end.Originated from a collaboration between researchers and community stakeholders, the CHRIS COVID-19 study aims at generating knowledge about the epidemiological, molecular, and genetic characterization of COVID-19 and its long-term sequelae.",
        "authors": [
            "Pattaro C",
            "Barbieri G",
            "Foco L",
            "Weichenberger CX",
            "Biasiotto R",
            "De Grandi A",
            "Fuchsberger C",
            "Egger C",
            "Amon VSC",
            "Hicks AA",
            "Mian M",
            "Mahlknecht A",
            "Lombardo S",
            "Meier H",
            "Weiss H",
            "Rainer R",
            "Dejaco C",
            "Weiss G",
            "Lavezzo E",
            "Crisanti A",
            "Pizzato M",
            "Domingues FS",
            "Mascalzoni D",
            "G\u00f6gele M",
            "Melotti R",
            "Pramstaller PP"
        ],
        "doi": "10.1080/20477724.2021.1978225",
        "source_study": [
            "CHRIS COVID-19"
        ],
        "ar": "303",
        "volume": "116",
        "issue": "2",
        "pages": "128-136",
        "pre": false,
        "pdate": "2021-10-13"
    },
    "10.1080/20477724.2023.2191232": {
        "title": "Determinants of SARS-CoV-2 nasopharyngeal testing in a rural community sample susceptible of first infection: the CHRIS COVID-19 study.",
        "journal": "Pathogens and global health",
        "year": "2023",
        "abstract": "To characterize COVID-19 epidemiology, numerous population-based studies have been undertaken to model the risk of SARS-CoV-2 infection. Less is known about what may drive the probability to undergo testing. Understanding how much testing is driven by contextual or individual conditions is important to delineate the role of individual behavior and to shape public health interventions and resource allocation. In the Val Venosta/Vinschgau district (South Tyrol, Italy), we conducted a population-representative longitudinal study on 697 individuals susceptible to first infection who completed 4,512 repeated online questionnaires at four-week intervals between September 2020 and May 2021. Mixed-effects logistic regression models were fitted to investigate associations of self-reported SARS-CoV-2 testing with individual characteristics (social, demographic, and biological) and contextual determinants. Testing was associated with month of reporting, reflecting the timing of both the pandemic intensity and public health interventions, COVID-19-related symptoms (odds ratio, OR:8.26; 95% confidence interval, CI:6.04-11.31), contacts with infected individuals within home (OR:7.47, 95%CI:3.81-14.62) or outside home (OR:9.87, 95%CI:5.78-16.85), and being retired (OR:0.50, 95%CI:0.34-0.73). Symptoms and next within- and outside-home contacts were the leading determinants of swab testing predisposition in the most acute phase of the pandemics. Testing was not associated with age, sex, education, comorbidities, or lifestyle factors. In the study area, contextual determinants reflecting the course of the pandemic were predominant compared to individual sociodemographic characteristics in explaining the SARS-CoV-2 probability of testing. Decision makers should evaluate whether the intended target groups were correctly prioritized by the testing campaign.",
        "authors": [
            "Giardiello D",
            "Melotti R",
            "Barbieri G",
            "G\u00f6gele M",
            "Weichenberger CX",
            "Foco L",
            "Bottigliengo D",
            "Barin L",
            "Lundin R",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1080/20477724.2023.2191232",
        "source_study": [
            "CHRIS COVID-19"
        ],
        "ar": "302",
        "volume": "117",
        "issue": "8",
        "pages": "744-753",
        "pre": false,
        "pdate": "2023-03-31"
    },
    "10.1038/s41586-022-05275-y": {
        "title": "A saturated map of common genetic variants associated with human height.",
        "journal": "Nature",
        "year": "2022",
        "abstract": "Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4\u2009million individuals of diverse ancestries, we show\u00a0that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90\u2009kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.",
        "authors": [
            "Yengo L",
            "Vedantam S",
            "Marouli E",
            "Sidorenko J",
            "Bartell E",
            "Sakaue S",
            "Graff M",
            "Eliasen AU",
            "Jiang Y",
            "Raghavan S",
            "Miao J",
            "Arias JD",
            "Graham SE",
            "Mukamel RE",
            "Spracklen CN",
            "Yin X",
            "Chen SH",
            "Ferreira T",
            "Highland HH",
            "Ji Y",
            "Karaderi T",
            "Lin K",
            "L\u00fcll K",
            "Malden DE",
            "Medina-Gomez C",
            "Machado M",
            "Moore A",
            "R\u00fceger S",
            "Sim X",
            "Vrieze S",
            "Ahluwalia TS",
            "Akiyama M",
            "Allison MA",
            "Alvarez M",
            "Andersen MK",
            "Ani A",
            "Appadurai V",
            "Arbeeva L",
            "Bhaskar S",
            "Bielak LF",
            "Bollepalli S",
            "Bonnycastle LL",
            "Bork-Jensen J",
            "Bradfield JP",
            "Bradford Y",
            "Braund PS",
            "Brody JA",
            "Burgdorf KS",
            "Cade BE",
            "Cai H",
            "Cai Q",
            "Campbell A",
            "Ca\u00f1adas-Garre M",
            "Catamo E",
            "Chai JF",
            "Chai X",
            "Chang LC",
            "Chang YC",
            "Chen CH",
            "Chesi A",
            "Choi SH",
            "Chung RH",
            "Cocca M",
            "Concas MP",
            "Couture C",
            "Cuellar-Partida G",
            "Danning R",
            "Daw EW",
            "Degenhard F",
            "Delgado GE",
            "Delitala A",
            "Demirkan A",
            "Deng X",
            "Devineni P",
            "Dietl A",
            "Dimitriou M",
            "Dimitrov L",
            "Dorajoo R",
            "Ekici AB",
            "Engmann JE",
            "Fairhurst-Hunter Z",
            "Farmaki AE",
            "Faul JD",
            "Fernandez-Lopez JC",
            "Forer L",
            "Francescatto M",
            "Freitag-Wolf S",
            "Fuchsberger C",
            "Galesloot TE",
            "Gao Y",
            "Gao Z",
            "Geller F",
            "Giannakopoulou O",
            "Giulianini F",
            "Gjesing AP",
            "Goel A",
            "Gordon SD",
            "Gorski M",
            "Grove J",
            "Guo X",
            "Gustafsson S",
            "Haessler J",
            "Hansen TF",
            "Havulinna AS",
            "Haworth SJ",
            "He J",
            "Heard-Costa N",
            "Hebbar P",
            "Hindy G",
            "Ho YA",
            "Hofer E",
            "Holliday E",
            "Horn K",
            "Hornsby WE",
            "Hottenga JJ",
            "Huang H",
            "Huang J",
            "Huerta-Chagoya A",
            "Huffman JE",
            "Hung YJ",
            "Huo S",
            "Hwang MY",
            "Iha H",
            "Ikeda DD",
            "Isono M",
            "Jackson AU",
            "J\u00e4ger S",
            "Jansen IE",
            "Johansson I",
            "Jonas JB",
            "Jonsson A",
            "J\u00f8rgensen T",
            "Kalafati IP",
            "Kanai M",
            "Kanoni S",
            "K\u00e5rhus LL",
            "Kasturiratne A",
            "Katsuya T",
            "Kawaguchi T",
            "Kember RL",
            "Kentistou KA",
            "Kim HN",
            "Kim YJ",
            "Kleber ME",
            "Knol MJ",
            "Kurbasic A",
            "Lauzon M",
            "Le P",
            "Lea R",
            "Lee JY",
            "Leonard HL",
            "Li SA",
            "Li X",
            "Li X",
            "Liang J",
            "Lin H",
            "Lin SY",
            "Liu J",
            "Liu X",
            "Lo KS",
            "Long J",
            "Lores-Motta L",
            "Luan J",
            "Lyssenko V",
            "Lyytik\u00e4inen LP",
            "Mahajan A",
            "Mamakou V",
            "Mangino M",
            "Manichaikul A",
            "Marten J",
            "Mattheisen M",
            "Mavarani L",
            "McDaid AF",
            "Meidtner K",
            "Melendez TL",
            "Mercader JM",
            "Milaneschi Y",
            "Miller JE",
            "Millwood IY",
            "Mishra PP",
            "Mitchell RE",
            "M\u00f8llehave LT",
            "Morgan A",
            "Mucha S",
            "Munz M",
            "Nakatochi M",
            "Nelson CP",
            "Nethander M",
            "Nho CW",
            "Nielsen AA",
            "Nolte IM",
            "Nongmaithem SS",
            "Noordam R",
            "Ntalla I",
            "Nutile T",
            "Pandit A",
            "Christofidou P",
            "P\u00e4rna K",
            "Pauper M",
            "Petersen ERB",
            "Petersen LV",
            "Pitk\u00e4nen N",
            "Pola\u0161ek O",
            "Poveda A",
            "Preuss MH",
            "Pyarajan S",
            "Raffield LM",
            "Rakugi H",
            "Ramirez J",
            "Rasheed A",
            "Raven D",
            "Rayner NW",
            "Riveros C",
            "Rohde R",
            "Ruggiero D",
            "Ruotsalainen SE",
            "Ryan KA",
            "Sabater-Lleal M",
            "Saxena R",
            "Scholz M",
            "Sendamarai A",
            "Shen B",
            "Shi J",
            "Shin JH",
            "Sidore C",
            "Sitlani CM",
            "Slieker RC",
            "Smit RAJ",
            "Smith AV",
            "Smith JA",
            "Smyth LJ",
            "Southam L",
            "Steinthorsdottir V",
            "Sun L",
            "Takeuchi F",
            "Tallapragada DSP",
            "Taylor KD",
            "Tayo BO",
            "Tcheandjieu C",
            "Terzikhan N",
            "Tesolin P",
            "Teumer A",
            "Theusch E",
            "Thompson DJ",
            "Thorleifsson G",
            "Timmers PRHJ",
            "Trompet S",
            "Turman C",
            "Vaccargiu S",
            "van der Laan SW",
            "van der Most PJ",
            "van Klinken JB",
            "van Setten J",
            "Verma SS",
            "Verweij N",
            "Veturi Y",
            "Wang CA",
            "Wang C",
            "Wang L",
            "Wang Z",
            "Warren HR",
            "Bin Wei W",
            "Wickremasinghe AR",
            "Wielscher M",
            "Wiggins KL",
            "Winsvold BS",
            "Wong A",
            "Wu Y",
            "Wuttke M",
            "Xia R",
            "Xie T",
            "Yamamoto K",
            "Yang J",
            "Yao J",
            "Young H",
            "Yousri NA",
            "Yu L",
            "Zeng L",
            "Zhang W",
            "Zhang X",
            "Zhao JH",
            "Zhao W",
            "Zhou W",
            "Zimmermann ME",
            "Zoledziewska M",
            "Adair LS",
            "Adams HHH",
            "Aguilar-Salinas CA",
            "Al-Mulla F",
            "Arnett DK",
            "Asselbergs FW",
            "\u00c5svold BO",
            "Attia J",
            "Banas B",
            "Bandinelli S",
            "Bennett DA",
            "Bergler T",
            "Bharadwaj D",
            "Biino G",
            "Bisgaard H",
            "Boerwinkle E",
            "B\u00f6ger CA",
            "B\u00f8nnelykke K",
            "Boomsma DI",
            "B\u00f8rglum AD",
            "Borja JB",
            "Bouchard C",
            "Bowden DW",
            "Brandslund I",
            "Brumpton B",
            "Buring JE",
            "Caulfield MJ",
            "Chambers JC",
            "Chandak GR",
            "Chanock SJ",
            "Chaturvedi N",
            "Chen YI",
            "Chen Z",
            "Cheng CY",
            "Christophersen IE",
            "Ciullo M",
            "Cole JW",
            "Collins FS",
            "Cooper RS",
            "Cruz M",
            "Cucca F",
            "Cupples LA",
            "Cutler MJ",
            "Damrauer SM",
            "Dantoft TM",
            "de Borst GJ",
            "de Groot LCPGM",
            "De Jager PL",
            "de Kleijn DPV",
            "Janaka de Silva H",
            "Dedoussis GV",
            "den Hollander AI",
            "Du S",
            "Easton DF",
            "Elders PJM",
            "Eliassen AH",
            "Ellinor PT",
            "Elmst\u00e5hl S",
            "Erdmann J",
            "Evans MK",
            "Fatkin D",
            "Feenstra B",
            "Feitosa MF",
            "Ferrucci L",
            "Ford I",
            "Fornage M",
            "Franke A",
            "Franks PW",
            "Freedman BI",
            "Gasparini P",
            "Gieger C",
            "Girotto G",
            "Goddard ME",
            "Golightly YM",
            "Gonzalez-Villalpando C",
            "Gordon-Larsen P",
            "Grallert H",
            "Grant SFA",
            "Grarup N",
            "Griffiths L",
            "Gudnason V",
            "Haiman C",
            "Hakonarson H",
            "Hansen T",
            "Hartman CA",
            "Hattersley AT",
            "Hayward C",
            "Heckbert SR",
            "Heng CK",
            "Hengstenberg C",
            "Hewitt AW",
            "Hishigaki H",
            "Hoyng CB",
            "Huang PL",
            "Huang W",
            "Hunt SC",
            "Hveem K",
            "Hypp\u00f6nen E",
            "Iacono WG",
            "Ichihara S",
            "Ikram MA",
            "Isasi CR",
            "Jackson RD",
            "Jarvelin MR",
            "Jin ZB",
            "J\u00f6ckel KH",
            "Joshi PK",
            "Jousilahti P",
            "Jukema JW",
            "K\u00e4h\u00f6nen M",
            "Kamatani Y",
            "Kang KD",
            "Kaprio J",
            "Kardia SLR",
            "Karpe F",
            "Kato N",
            "Kee F",
            "Kessler T",
            "Khera AV",
            "Khor CC",
            "Kiemeney LALM",
            "Kim BJ",
            "Kim EK",
            "Kim HL",
            "Kirchhof P",
            "Kivimaki M",
            "Koh WP",
            "Koistinen HA",
            "Kolovou GD",
            "Kooner JS",
            "Kooperberg C",
            "K\u00f6ttgen A",
            "Kovacs P",
            "Kraaijeveld A",
            "Kraft P",
            "Krauss RM",
            "Kumari M",
            "Kutalik Z",
            "Laakso M",
            "Lange LA",
            "Langenberg C",
            "Launer LJ",
            "Le Marchand L",
            "Lee H",
            "Lee NR",
            "Lehtim\u00e4ki T",
            "Li H",
            "Li L",
            "Lieb W",
            "Lin X",
            "Lind L",
            "Linneberg A",
            "Liu CT",
            "Liu J",
            "Loeffler M",
            "London B",
            "Lubitz SA",
            "Lye SJ",
            "Mackey DA",
            "M\u00e4gi R",
            "Magnusson PKE",
            "Marcus GM",
            "Vidal PM",
            "Martin NG",
            "M\u00e4rz W",
            "Matsuda F",
            "McGarrah RW",
            "McGue M",
            "McKnight AJ",
            "Medland SE",
            "Mellstr\u00f6m D",
            "Metspalu A",
            "Mitchell BD",
            "Mitchell P",
            "Mook-Kanamori DO",
            "Morris AD",
            "Mucci LA",
            "Munroe PB",
            "Nalls MA",
            "Nazarian S",
            "Nelson AE",
            "Neville MJ",
            "Newton-Cheh C",
            "Nielsen CS",
            "N\u00f6then MM",
            "Ohlsson C",
            "Oldehinkel AJ",
            "Orozco L",
            "Pahkala K",
            "Pajukanta P",
            "Palmer CNA",
            "Parra EJ",
            "Pattaro C",
            "Pedersen O",
            "Pennell CE",
            "Penninx BWJH",
            "Perusse L",
            "Peters A",
            "Peyser PA",
            "Porteous DJ",
            "Posthuma D",
            "Power C",
            "Pramstaller PP",
            "Province MA",
            "Qi Q",
            "Qu J",
            "Rader DJ",
            "Raitakari OT",
            "Ralhan S",
            "Rallidis LS",
            "Rao DC",
            "Redline S",
            "Reilly DF",
            "Reiner AP",
            "Rhee SY",
            "Ridker PM",
            "Rienstra M",
            "Ripatti S",
            "Ritchie MD",
            "Roden DM",
            "Rosendaal FR",
            "Rotter JI",
            "Rudan I",
            "Rutters F",
            "Sabanayagam C",
            "Saleheen D",
            "Salomaa V",
            "Samani NJ",
            "Sanghera DK",
            "Sattar N",
            "Schmidt B",
            "Schmidt H",
            "Schmidt R",
            "Schulze MB",
            "Schunkert H",
            "Scott LJ",
            "Scott RJ",
            "Sever P",
            "Shiroma EJ",
            "Shoemaker MB",
            "Shu XO",
            "Simonsick EM",
            "Sims M",
            "Singh JR",
            "Singleton AB",
            "Sinner MF",
            "Smith JG",
            "Snieder H",
            "Spector TD",
            "Stampfer MJ",
            "Stark KJ",
            "Strachan DP",
            "'t Hart LM",
            "Tabara Y",
            "Tang H",
            "Tardif JC",
            "Thanaraj TA",
            "Timpson NJ",
            "T\u00f6njes A",
            "Tremblay A",
            "Tuomi T",
            "Tuomilehto J",
            "Tusi\u00e9-Luna MT",
            "Uitterlinden AG",
            "van Dam RM",
            "van der Harst P",
            "Van der Velde N",
            "van Duijn CM",
            "van Schoor NM",
            "Vitart V",
            "V\u00f6lker U",
            "Vollenweider P",
            "V\u00f6lzke H",
            "Wacher-Rodarte NH",
            "Walker M",
            "Wang YX",
            "Wareham NJ",
            "Watanabe RM",
            "Watkins H",
            "Weir DR",
            "Werge TM",
            "Widen E",
            "Wilkens LR",
            "Willemsen G",
            "Willett WC",
            "Wilson JF",
            "Wong TY",
            "Woo JT",
            "Wright AF",
            "Wu JY",
            "Xu H",
            "Yajnik CS",
            "Yokota M",
            "Yuan JM",
            "Zeggini E",
            "Zemel BS",
            "Zheng W",
            "Zhu X",
            "Zmuda JM",
            "Zonderman AB",
            "Zwart JA",
            "Chasman DI",
            "Cho YS",
            "Heid IM",
            "McCarthy MI",
            "Ng MCY",
            "O'Donnell CJ",
            "Rivadeneira F",
            "Thorsteinsdottir U",
            "Sun YV",
            "Tai ES",
            "Boehnke M",
            "Deloukas P",
            "Justice AE",
            "Lindgren CM",
            "Loos RJF",
            "Mohlke KL",
            "North KE",
            "Stefansson K",
            "Walters RG",
            "Winkler TW",
            "Young KL",
            "Loh PR",
            "Yang J",
            "Esko T",
            "Assimes TL",
            "Auton A",
            "Abecasis GR",
            "Willer CJ",
            "Locke AE",
            "Berndt SI",
            "Lettre G",
            "Frayling TM",
            "Okada Y",
            "Wood AR",
            "Visscher PM",
            "Hirschhorn JN"
        ],
        "doi": "10.1038/s41586-022-05275-y",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "301",
        "volume": "610",
        "issue": "7933",
        "pages": "704-712",
        "pre": false,
        "pdate": "2022-10-13"
    },
    "10.3390/metabo12030205": {
        "title": "Age, Sex, Body Mass Index, Diet and Menopause Related Metabolites in a Large Homogeneous Alpine Cohort.",
        "journal": "Metabolites",
        "year": "2022",
        "abstract": "Metabolomics in human serum samples provide a snapshot of the current metabolic state of an individuum. Metabolite concentrations are influenced by both genetic and environmental factors. Concentrations of certain metabolites can further depend on age, sex, menopause, and diet of study participants. A better understanding of these relationships is pivotal for the planning of metabolomics studies involving human subjects and interpretation of their results. We generated one of the largest single-site targeted metabolomics data sets consisting of 175 quantified metabolites in 6872 study participants. We identified metabolites significantly associated with age, sex, body mass index, diet, and menopausal status. While most of our results agree with previous large-scale studies, we also found novel associations including serotonin as a sex and BMI-related metabolite and sarcosine and C2 carnitine showing significantly higher concentrations in post-menopausal women. Finally, we observed strong associations between higher consumption of food items and certain metabolites, mostly phosphatidylcholines and lysophosphatidylcholines. Most, and the strongest, relationships were found for habitual meat intake while no significant relationships were found for most fruits, vegetables, and grain products. Summarizing, our results reconfirm findings from previous population-based studies on an independent cohort. Together, these findings will ultimately enable the consolidation of sets of metabolites which are related to age, sex, BMI, and menopause as well as to participants' diet.",
        "authors": [
            "Verri Hernandes V",
            "Dordevic N",
            "Hantikainen EM",
            "Sigurdsson BB",
            "Sm\u00e1rason SV",
            "Garcia-Larsen V",
            "G\u00f6gele M",
            "Caprioli G",
            "Bozzolan I",
            "Pramstaller PP",
            "Rainer J"
        ],
        "doi": "10.3390/metabo12030205",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "298",
        "volume": "12",
        "issue": "3",
        "pages": "",
        "pre": false,
        "pdate": "2022-03-25"
    },
    "10.1038/s42003-022-03448-z": {
        "title": "Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.",
        "journal": "Communications biology",
        "year": "2022",
        "abstract": "Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n<sub>DM</sub>\u2009=\u2009178,691, n<sub>noDM</sub>\u2009=\u20091,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including *CUBN*) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.",
        "authors": [
            "Winkler TW",
            "Rasheed H",
            "Teumer A",
            "Gorski M",
            "Rowan BX",
            "Stanzick KJ",
            "Thomas LF",
            "Tin A",
            "Hoppmann A",
            "Chu AY",
            "Tayo B",
            "Thio CHL",
            "Cusi D",
            "Chai JF",
            "Sieber KB",
            "Horn K",
            "Li M",
            "Scholz M",
            "Cocca M",
            "Wuttke M",
            "van der Most PJ",
            "Yang Q",
            "Ghasemi S",
            "Nutile T",
            "Li Y",
            "Pontali G",
            "G\u00fcnther F",
            "Dehghan A",
            "Correa A",
            "Parsa A",
            "Feresin A",
            "de Vries APJ",
            "Zonderman AB",
            "Smith AV",
            "Oldehinkel AJ",
            "De Grandi A",
            "Rosenkranz AR",
            "Franke A",
            "Teren A",
            "Metspalu A",
            "Hicks AA",
            "Morris AP",
            "T\u00f6njes A",
            "Morgan A",
            "Podgornaia AI",
            "Peters A",
            "K\u00f6rner A",
            "Mahajan A",
            "Campbell A",
            "Freedman BI",
            "Spedicati B",
            "Ponte B",
            "Sch\u00f6ttker B",
            "Brumpton B",
            "Banas B",
            "Kr\u00e4mer BK",
            "Jung B",
            "\u00c5svold BO",
            "Smith BH",
            "Ning B",
            "Penninx BWJH",
            "Vanderwerff BR",
            "Psaty BM",
            "Kammerer CM",
            "Langefeld CD",
            "Hayward C",
            "Spracklen CN",
            "Robinson-Cohen C",
            "Hartman CA",
            "Lindgren CM",
            "Wang C",
            "Sabanayagam C",
            "Heng CK",
            "Lanzani C",
            "Khor CC",
            "Cheng CY",
            "Fuchsberger C",
            "Gieger C",
            "Shaffer CM",
            "Schulz CA",
            "Willer CJ",
            "Chasman DI",
            "Gudbjartsson DF",
            "Ruggiero D",
            "Toniolo D",
            "Czamara D",
            "Porteous DJ",
            "Waterworth DM",
            "Mascalzoni D",
            "Mook-Kanamori DO",
            "Reilly DF",
            "Daw EW",
            "Hofer E",
            "Boerwinkle E",
            "Salvi E",
            "Bottinger EP",
            "Tai ES",
            "Catamo E",
            "Rizzi F",
            "Guo F",
            "Rivadeneira F",
            "Guilianini F",
            "Sveinbjornsson G",
            "Ehret G",
            "Waeber G",
            "Biino G",
            "Girotto G",
            "Pistis G",
            "Nadkarni GN",
            "Delgado GE",
            "Montgomery GW",
            "Snieder H",
            "Campbell H",
            "White HD",
            "Gao H",
            "Stringham HM",
            "Schmidt H",
            "Li H",
            "Brenner H",
            "Holm H",
            "Kirsten H",
            "Kramer H",
            "Rudan I",
            "Nolte IM",
            "Tzoulaki I",
            "Olafsson I",
            "Martins J",
            "Cook JP",
            "Wilson JF",
            "Halbritter J",
            "Felix JF",
            "Divers J",
            "Kooner JS",
            "Lee JJ",
            "O'Connell J",
            "Rotter JI",
            "Liu J",
            "Xu J",
            "Thiery J",
            "\u00c4rnl\u00f6v J",
            "Kuusisto J",
            "Jakobsdottir J",
            "Tremblay J",
            "Chambers JC",
            "Whitfield JB",
            "Gaziano JM",
            "Marten J",
            "Coresh J",
            "Jonas JB",
            "Mychaleckyj JC",
            "Christensen K",
            "Eckardt KU",
            "Mohlke KL",
            "Endlich K",
            "Dittrich K",
            "Ryan KA",
            "Rice KM",
            "Taylor KD",
            "Ho K",
            "Nikus K",
            "Matsuda K",
            "Strauch K",
            "Miliku K",
            "Hveem K",
            "Lind L",
            "Wallentin L",
            "Yerges-Armstrong LM",
            "Raffield LM",
            "Phillips LS",
            "Launer LJ",
            "Lyytik\u00e4inen LP",
            "Lange LA",
            "Citterio L",
            "Klaric L",
            "Ikram MA",
            "Ising M",
            "Kleber ME",
            "Francescatto M",
            "Concas MP",
            "Ciullo M",
            "Piratsu M",
            "Orho-Melander M",
            "Laakso M",
            "Loeffler M",
            "Perola M",
            "de Borst MH",
            "G\u00f6gele M",
            "Bianca M",
            "Lukas MA",
            "Feitosa MF",
            "Biggs ML",
            "Wojczynski MK",
            "Kavousi M",
            "Kanai M",
            "Akiyama M",
            "Yasuda M",
            "Nauck M",
            "Waldenberger M",
            "Chee ML",
            "Chee ML",
            "Boehnke M",
            "Preuss MH",
            "Stumvoll M",
            "Province MA",
            "Evans MK",
            "O'Donoghue ML",
            "Kubo M",
            "K\u00e4h\u00f6nen M",
            "Kastarinen M",
            "Nalls MA",
            "Kuokkanen M",
            "Ghanbari M",
            "Bochud M",
            "Josyula NS",
            "Martin NG",
            "Tan NYQ",
            "Palmer ND",
            "Pirastu N",
            "Schupf N",
            "Verweij N",
            "Hutri-K\u00e4h\u00f6nen N",
            "Mononen N",
            "Bansal N",
            "Devuyst O",
            "Melander O",
            "Raitakari OT",
            "Polasek O",
            "Manunta P",
            "Gasparini P",
            "Mishra PP",
            "Sulem P",
            "Magnusson PKE",
            "Elliott P",
            "Ridker PM",
            "Hamet P",
            "Svensson PO",
            "Joshi PK",
            "Kovacs P",
            "Pramstaller PP",
            "Rossing P",
            "Vollenweider P",
            "van der Harst P",
            "Dorajoo R",
            "Sim RZH",
            "Burkhardt R",
            "Tao R",
            "Noordam R",
            "M\u00e4gi R",
            "Schmidt R",
            "de Mutsert R",
            "Rueedi R",
            "van Dam RM",
            "Carroll RJ",
            "Gansevoort RT",
            "Loos RJF",
            "Felicita SC",
            "Sedaghat S",
            "Padmanabhan S",
            "Freitag-Wolf S",
            "Pendergrass SA",
            "Graham SE",
            "Gordon SD",
            "Hwang SJ",
            "Kerr SM",
            "Vaccargiu S",
            "Patil SB",
            "Hallan S",
            "Bakker SJL",
            "Lim SC",
            "Lucae S",
            "Vogelezang S",
            "Bergmann S",
            "Corre T",
            "Ahluwalia TS",
            "Lehtim\u00e4ki T",
            "Boutin TS",
            "Meitinger T",
            "Wong TY",
            "Bergler T",
            "Rabelink TJ",
            "Esko T",
            "Haller T",
            "Thorsteinsdottir U",
            "V\u00f6lker U",
            "Foo VHX",
            "Salomaa V",
            "Vitart V",
            "Giedraitis V",
            "Gudnason V",
            "Jaddoe VWV",
            "Huang W",
            "Zhang W",
            "Wei WB",
            "Kiess W",
            "M\u00e4rz W",
            "Koenig W",
            "Lieb W",
            "Gao X",
            "Sim X",
            "Wang YX",
            "Friedlander Y",
            "Tham YC",
            "Kamatani Y",
            "Okada Y",
            "Milaneschi Y",
            "Yu Z",
            "Stark KJ",
            "Stefansson K",
            "B\u00f6ger CA",
            "Hung AM",
            "Kronenberg F",
            "K\u00f6ttgen A",
            "Pattaro C",
            "Heid IM"
        ],
        "doi": "10.1038/s42003-022-03448-z",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "291",
        "volume": "5",
        "issue": "1",
        "pages": "580",
        "pre": false,
        "pdate": "2022-06-14"
    },
    "10.1016/j.scr.2022.102692": {
        "title": "Generation and characterization of induced pluripotent stem cell (iPSC) lines of two asymptomatic individuals carrying a heterozygous exon 7 deletion in Parkin (PRKN) and two non-carriers from the same family.",
        "journal": "Stem cell research",
        "year": "2022",
        "abstract": "Mutations in the *Parkin* (*PRKN*) gene are the most frequent known cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous mutations might predispose to disease with a highly reduced penetrance. We generated iPSC lines from two individuals carrying a heterozygous deletion of exon 7 in the *PRKN* gene and two controls from the same family. PBMCs were reprogrammed using non-integrating episomal plasmids. The iPSC lines exhibit expression of pluripotency markers, the potential to differentiate into the three germ layers, and a stable karyotype. These lines will serve to study mechanisms of reduced penetrance in heterozygous *PRKN* mutation carriers.",
        "authors": [
            "Castelo Rueda MP",
            "Gilmozzi V",
            "Riekschnitz DA",
            "Di Segni M",
            "Silipigni R",
            "Pramstaller PP",
            "Hicks AA",
            "Pichler I",
            "Zanon A"
        ],
        "doi": "10.1016/j.scr.2022.102692",
        "source_study": [
            "CHRIS PAREGEN"
        ],
        "ar": "285",
        "volume": "60",
        "issue": "",
        "pages": "102692",
        "pre": false,
        "pdate": "2022-02-06"
    },
    "10.3390/biom11111663": {
        "title": "Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study.",
        "journal": "Biomolecules",
        "year": "2021",
        "abstract": "Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (*p*-value < 5 \u00d7 10<sup>-8</sup>) around SNPs rs745582874, next to gene *PBX1*, and rs768476991, within gene *PCCA*, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (*p*-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.",
        "authors": [
            "Emmert DB",
            "Vukovic V",
            "Dordevic N",
            "Weichenberger CX",
            "Losi C",
            "D'Elia Y",
            "Volpato C",
            "Hernandes VV",
            "G\u00f6gele M",
            "Foco L",
            "Pontali G",
            "Mascalzoni D",
            "Domingues FS",
            "Paulmichl R",
            "Pramstaller PP",
            "Pattaro C",
            "Rossini A",
            "Rainer J",
            "Fuchsberger C",
            "De Bortoli M"
        ],
        "doi": "10.3390/biom11111663",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "277",
        "volume": "11",
        "issue": "11",
        "pages": "",
        "pre": false,
        "pdate": "2021-11-28"
    },
    "10.3389/fneur.2021.706145": {
        "title": "Frequency of Heterozygous Parkin (PRKN) Variants and Penetrance of Parkinson's Disease Risk Markers in the Population-Based CHRIS Cohort.",
        "journal": "Frontiers in neurology",
        "year": "2021",
        "abstract": "Mutations in the *Parkin* (*PRKN*) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous *PRKN* mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimates of the penetrance of these variants, and to investigate, which clinical and biochemical markers are present in carriers and thus potentially useful for identifying those individuals at greater risk of developing clinical symptoms later in life. In the present study, we ascertained the frequency of heterozygous *PRKN* mutation carriers in a large population sample of the Cooperative Health Research in South Tyrol (CHRIS) study, and screened for reported PD risk markers. 164 confirmed heterozygous *PRKN* mutation carriers were compared with 2,582 controls. A higher number of heterozygous mutation carriers reported a detectable increase in an akinesia-related phenotype, and a higher percentage of carriers had manifested diabetes. We also observed lower resting heart rate in the *PRKN* mutation carriers. Extending our risk analyses to a larger number of potential carriers and non-carriers using genotype imputation (n = 299 carriers and n = 7,127 non-carriers), from previously published biomarkers we also observed a higher neutrophil-to-lymphocyte ratio (NLR) and lower serum albumin and sodium levels in the heterozygous *PRKN* variant carriers. These results identify a set of biomarkers that might be useful either individually or as an ensemble to identify variant carriers at greater risk of health issues due to carrier status.",
        "authors": [
            "Castelo Rueda MP",
            "Raftopoulou A",
            "G\u00f6gele M",
            "Borsche M",
            "Emmert D",
            "Fuchsberger C",
            "Hantikainen EM",
            "Vukovic V",
            "Klein C",
            "Pramstaller PP",
            "Pichler I",
            "Hicks AA"
        ],
        "doi": "10.3389/fneur.2021.706145",
        "source_study": [
            "CHRIS PAREGEN",
            "CHRIS baseline"
        ],
        "ar": "273",
        "volume": "12",
        "issue": "",
        "pages": "706145",
        "pre": false,
        "pdate": "2021-08-27"
    },
    "10.1038/s41431-022-01160-4": {
        "title": "Ten years of dynamic consent in the CHRIS study: informed consent as a dynamic process.",
        "journal": "European journal of human genetics",
        "year": "2022",
        "abstract": "The Cooperative Health Research in South Tyrol (CHRIS) is a longitudinal study in Northern Italy, using dynamic consent since its inception in 2011. The CHRIS study collects health data and biosamples for research, and foresees regular follow-ups over time. We describe the experience with the CHRIS study dynamic consent, providing an overview of its conceptualization and implementation, and of the participant-centered strategies used to assess and improve the process, directly linked to participation and communication. In order to comply with high ethical standards and to allow broadness in the areas of research, CHRIS dynamic consent was conceived as an interactive process: based on a strong governance and an ongoing tailored communication with participants, it aims to promote autonomy and to develop a trust-based engaged relationship with participants, also relevant for retention. Built within an online platform, the consent allows granular choices, which can be changed over time. In a process of co-production, participants views have been investigated and kept into account in policy development. Participants showed a high degree of participation, thus enabling the consolidation of the CHRIS resources. Even though a low change rate was reported in the baseline, participants valued the possibility of changing their informed consent choices. Communication (language-tailored, ongoing, multimedia) was important for participants, and for participation and retention. In our experience, dynamic consent was proven to be a flexible consent model, which allowed to meet ethical and legal standards for participation in research, and to accommodate participants' and researchers' needs.",
        "authors": [
            "Mascalzoni D",
            "Melotti R",
            "Pattaro C",
            "Pramstaller PP",
            "G\u00f6gele M",
            "De Grandi A",
            "Biasiotto R"
        ],
        "doi": "10.1038/s41431-022-01160-4",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "262",
        "volume": "30",
        "issue": "12",
        "pages": "1391-1397",
        "pre": false,
        "pdate": "2022-09-07"
    },
    "10.1016/j.numecd.2021.08.037": {
        "title": "Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes-The Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study.",
        "journal": "Nutrition, metabolism, and cardiovascular diseases",
        "year": "2021",
        "abstract": "**Background and aims**<br> Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD), both with and without type 2 diabetes mellitus (T2DM). Cardiac autonomic dysfunction is a risk factor for CVD morbidity and mortality. The aim of this pilot study was to assess whether there is an association between NAFLD and impaired cardiac autonomic function. <br>**Methods and results**<br> Among the first 4979 participants from the Cooperative Health Research in South Tyrol (CHRIS) study, we randomly recruited 173 individuals with T2DM and 183 age- and sex-matched nondiabetic controls. Participants underwent ultrasonography and vibration-controlled transient elastography (Fibroscan\u00ae, Echosens) to assess hepatic steatosis and liver stiffness. The low-to-high-frequency (LF/HF) power ratio and other heart rate variability (HRV) measures were calculated from a 20-min resting electrocardiogram (ECG) to derive a measure of cardiac sympathetic/parasympathetic imbalance. Among the 356 individuals recruited for the study, 117 had NAFLD and T2DM, 56 had T2DM alone, 68 had NAFLD alone, and 115 subjects had neither condition. Individuals with T2DM and NAFLD (adjusted odds ratio [OR] 4.29, 95% confidence intervals [CI] 1.90-10.6) and individuals with NAFLD alone (adjusted OR 3.41, 95% CI 1.59-7.29), but not those with T2DM alone, had a substantially increased risk of having cardiac sympathetic/parasympathetic imbalance, compared with those without NAFLD and T2DM. Logistic regression models were adjusted for age, sex, body mass index (BMI), hypertension, dyslipidemia, insulin resistance, hemoglobin A1c (HbA1c), C-reactive protein (CRP), and Fibroscan\u00ae-measured liver stiffness. <br>**Conclusions**<br> NAFLD was associated with cardiac sympathetic/parasympathetic imbalance, regardless of the presence or absence of T2DM, liver stiffness, and other potential confounding factors.",
        "authors": [
            "Targher G",
            "Mantovani A",
            "Grander C",
            "Foco L",
            "Motta B",
            "Byrne CD",
            "Pramstaller PP",
            "Tilg H"
        ],
        "doi": "10.1016/j.numecd.2021.08.037",
        "source_study": [
            "CHRIS NAFLD"
        ],
        "ar": "258",
        "volume": "31",
        "issue": "12",
        "pages": "3464-3473",
        "pre": false,
        "pdate": "2021-10-11"
    },
    "10.1038/s41586-021-04064-3": {
        "title": "The power of genetic diversity in genome-wide association studies of lipids.",
        "journal": "Nature",
        "year": "2021",
        "abstract": "Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wide association studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65\u2009million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately\u2009295,000 individuals from 7\u2009ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine, we anticipate that increased diversity of participants will lead to more accurate and equitable application of polygenic scores in clinical practice.",
        "authors": [
            "Graham SE",
            "Clarke SL",
            "Wu KH",
            "Kanoni S",
            "Zajac GJM",
            "Ramdas S",
            "Surakka I",
            "Ntalla I",
            "Vedantam S",
            "Winkler TW",
            "Locke AE",
            "Marouli E",
            "Hwang MY",
            "Han S",
            "Narita A",
            "Choudhury A",
            "Bentley AR",
            "Ekoru K",
            "Verma A",
            "Trivedi B",
            "Martin HC",
            "Hunt KA",
            "Hui Q",
            "Klarin D",
            "Zhu X",
            "Thorleifsson G",
            "Helgadottir A",
            "Gudbjartsson DF",
            "Holm H",
            "Olafsson I",
            "Akiyama M",
            "Sakaue S",
            "Terao C",
            "Kanai M",
            "Zhou W",
            "Brumpton BM",
            "Rasheed H",
            "Ruotsalainen SE",
            "Havulinna AS",
            "Veturi Y",
            "Feng Q",
            "Rosenthal EA",
            "Lingren T",
            "Pacheco JA",
            "Pendergrass SA",
            "Haessler J",
            "Giulianini F",
            "Bradford Y",
            "Miller JE",
            "Campbell A",
            "Lin K",
            "Millwood IY",
            "Hindy G",
            "Rasheed A",
            "Faul JD",
            "Zhao W",
            "Weir DR",
            "Turman C",
            "Huang H",
            "Graff M",
            "Mahajan A",
            "Brown MR",
            "Zhang W",
            "Yu K",
            "Schmidt EM",
            "Pandit A",
            "Gustafsson S",
            "Yin X",
            "Luan J",
            "Zhao JH",
            "Matsuda F",
            "Jang HM",
            "Yoon K",
            "Medina-Gomez C",
            "Pitsillides A",
            "Hottenga JJ",
            "Willemsen G",
            "Wood AR",
            "Ji Y",
            "Gao Z",
            "Haworth S",
            "Mitchell RE",
            "Chai JF",
            "Aadahl M",
            "Yao J",
            "Manichaikul A",
            "Warren HR",
            "Ramirez J",
            "Bork-Jensen J",
            "K\u00e5rhus LL",
            "Goel A",
            "Sabater-Lleal M",
            "Noordam R",
            "Sidore C",
            "Fiorillo E",
            "McDaid AF",
            "Marques-Vidal P",
            "Wielscher M",
            "Trompet S",
            "Sattar N",
            "M\u00f8llehave LT",
            "Thuesen BH",
            "Munz M",
            "Zeng L",
            "Huang J",
            "Yang B",
            "Poveda A",
            "Kurbasic A",
            "Lamina C",
            "Forer L",
            "Scholz M",
            "Galesloot TE",
            "Bradfield JP",
            "Daw EW",
            "Zmuda JM",
            "Mitchell JS",
            "Fuchsberger C",
            "Christensen H",
            "Brody JA",
            "Feitosa MF",
            "Wojczynski MK",
            "Preuss M",
            "Mangino M",
            "Christofidou P",
            "Verweij N",
            "Benjamins JW",
            "Engmann J",
            "Kember RL",
            "Slieker RC",
            "Lo KS",
            "Zilhao NR",
            "Le P",
            "Kleber ME",
            "Delgado GE",
            "Huo S",
            "Ikeda DD",
            "Iha H",
            "Yang J",
            "Liu J",
            "Leonard HL",
            "Marten J",
            "Schmidt B",
            "Arendt M",
            "Smyth LJ",
            "Ca\u00f1adas-Garre M",
            "Wang C",
            "Nakatochi M",
            "Wong A",
            "Hutri-K\u00e4h\u00f6nen N",
            "Sim X",
            "Xia R",
            "Huerta-Chagoya A",
            "Fernandez-Lopez JC",
            "Lyssenko V",
            "Ahmed M",
            "Jackson AU",
            "Yousri NA",
            "Irvin MR",
            "Oldmeadow C",
            "Kim HN",
            "Ryu S",
            "Timmers PRHJ",
            "Arbeeva L",
            "Dorajoo R",
            "Lange LA",
            "Chai X",
            "Prasad G",
            "Lor\u00e9s-Motta L",
            "Pauper M",
            "Long J",
            "Li X",
            "Theusch E",
            "Takeuchi F",
            "Spracklen CN",
            "Loukola A",
            "Bollepalli S",
            "Warner SC",
            "Wang YX",
            "Wei WB",
            "Nutile T",
            "Ruggiero D",
            "Sung YJ",
            "Hung YJ",
            "Chen S",
            "Liu F",
            "Yang J",
            "Kentistou KA",
            "Gorski M",
            "Brumat M",
            "Meidtner K",
            "Bielak LF",
            "Smith JA",
            "Hebbar P",
            "Farmaki AE",
            "Hofer E",
            "Lin M",
            "Xue C",
            "Zhang J",
            "Concas MP",
            "Vaccargiu S",
            "van der Most PJ",
            "Pitk\u00e4nen N",
            "Cade BE",
            "Lee J",
            "van der Laan SW",
            "Chitrala KN",
            "Weiss S",
            "Zimmermann ME",
            "Lee JY",
            "Choi HS",
            "Nethander M",
            "Freitag-Wolf S",
            "Southam L",
            "Rayner NW",
            "Wang CA",
            "Lin SY",
            "Wang JS",
            "Couture C",
            "Lyytik\u00e4inen LP",
            "Nikus K",
            "Cuellar-Partida G",
            "Vestergaard H",
            "Hildalgo B",
            "Giannakopoulou O",
            "Cai Q",
            "Obura MO",
            "van Setten J",
            "Li X",
            "Schwander K",
            "Terzikhan N",
            "Shin JH",
            "Jackson RD",
            "Reiner AP",
            "Martin LW",
            "Chen Z",
            "Li L",
            "Highland HM",
            "Young KL",
            "Kawaguchi T",
            "Thiery J",
            "Bis JC",
            "Nadkarni GN",
            "Launer LJ",
            "Li H",
            "Nalls MA",
            "Raitakari OT",
            "Ichihara S",
            "Wild SH",
            "Nelson CP",
            "Campbell H",
            "J\u00e4ger S",
            "Nabika T",
            "Al-Mulla F",
            "Niinikoski H",
            "Braund PS",
            "Kolcic I",
            "Kovacs P",
            "Giardoglou T",
            "Katsuya T",
            "Bhatti KF",
            "de Kleijn D",
            "de Borst GJ",
            "Kim EK",
            "Adams HHH",
            "Ikram MA",
            "Zhu X",
            "Asselbergs FW",
            "Kraaijeveld AO",
            "Beulens JWJ",
            "Shu XO",
            "Rallidis LS",
            "Pedersen O",
            "Hansen T",
            "Mitchell P",
            "Hewitt AW",
            "K\u00e4h\u00f6nen M",
            "P\u00e9russe L",
            "Bouchard C",
            "T\u00f6njes A",
            "Chen YI",
            "Pennell CE",
            "Mori TA",
            "Lieb W",
            "Franke A",
            "Ohlsson C",
            "Mellstr\u00f6m D",
            "Cho YS",
            "Lee H",
            "Yuan JM",
            "Koh WP",
            "Rhee SY",
            "Woo JT",
            "Heid IM",
            "Stark KJ",
            "V\u00f6lzke H",
            "Homuth G",
            "Evans MK",
            "Zonderman AB",
            "Polasek O",
            "Pasterkamp G",
            "Hoefer IE",
            "Redline S",
            "Pahkala K",
            "Oldehinkel AJ",
            "Snieder H",
            "Biino G",
            "Schmidt R",
            "Schmidt H",
            "Chen YE",
            "Bandinelli S",
            "Dedoussis G",
            "Thanaraj TA",
            "Kardia SLR",
            "Kato N",
            "Schulze MB",
            "Girotto G",
            "Jung B",
            "B\u00f6ger CA",
            "Joshi PK",
            "Bennett DA",
            "De Jager PL",
            "Lu X",
            "Mamakou V",
            "Brown M",
            "Caulfield MJ",
            "Munroe PB",
            "Guo X",
            "Ciullo M",
            "Jonas JB",
            "Samani NJ",
            "Kaprio J",
            "Pajukanta P",
            "Adair LS",
            "Bechayda SA",
            "de Silva HJ",
            "Wickremasinghe AR",
            "Krauss RM",
            "Wu JY",
            "Zheng W",
            "den Hollander AI",
            "Bharadwaj D",
            "Correa A",
            "Wilson JG",
            "Lind L",
            "Heng CK",
            "Nelson AE",
            "Golightly YM",
            "Wilson JF",
            "Penninx B",
            "Kim HL",
            "Attia J",
            "Scott RJ",
            "Rao DC",
            "Arnett DK",
            "Hunt SC",
            "Walker M",
            "Koistinen HA",
            "Chandak GR",
            "Yajnik CS",
            "Mercader JM",
            "Tusi\u00e9-Luna T",
            "Aguilar-Salinas CA",
            "Villalpando CG",
            "Orozco L",
            "Fornage M",
            "Tai ES",
            "van Dam RM",
            "Lehtim\u00e4ki T",
            "Chaturvedi N",
            "Yokota M",
            "Liu J",
            "Reilly DF",
            "McKnight AJ",
            "Kee F",
            "J\u00f6ckel KH",
            "McCarthy MI",
            "Palmer CNA",
            "Vitart V",
            "Hayward C",
            "Simonsick E",
            "van Duijn CM",
            "Lu F",
            "Qu J",
            "Hishigaki H",
            "Lin X",
            "M\u00e4rz W",
            "Parra EJ",
            "Cruz M",
            "Gudnason V",
            "Tardif JC",
            "Lettre G",
            "'t Hart LM",
            "Elders PJM",
            "Damrauer SM",
            "Kumari M",
            "Kivimaki M",
            "van der Harst P",
            "Spector TD",
            "Loos RJF",
            "Province MA",
            "Psaty BM",
            "Brandslund I",
            "Pramstaller PP",
            "Christensen K",
            "Ripatti S",
            "Wid\u00e9n E",
            "Hakonarson H",
            "Grant SFA",
            "Kiemeney LALM",
            "de Graaf J",
            "Loeffler M",
            "Kronenberg F",
            "Gu D",
            "Erdmann J",
            "Schunkert H",
            "Franks PW",
            "Linneberg A",
            "Jukema JW",
            "Khera AV",
            "M\u00e4nnikk\u00f6 M",
            "Jarvelin MR",
            "Kutalik Z",
            "Cucca F",
            "Mook-Kanamori DO",
            "van Dijk KW",
            "Watkins H",
            "Strachan DP",
            "Grarup N",
            "Sever P",
            "Poulter N",
            "Rotter JI",
            "Dantoft TM",
            "Karpe F",
            "Neville MJ",
            "Timpson NJ",
            "Cheng CY",
            "Wong TY",
            "Khor CC",
            "Sabanayagam C",
            "Peters A",
            "Gieger C",
            "Hattersley AT",
            "Pedersen NL",
            "Magnusson PKE",
            "Boomsma DI",
            "de Geus EJC",
            "Cupples LA",
            "van Meurs JBJ",
            "Ghanbari M",
            "Gordon-Larsen P",
            "Huang W",
            "Kim YJ",
            "Tabara Y",
            "Wareham NJ",
            "Langenberg C",
            "Zeggini E",
            "Kuusisto J",
            "Laakso M",
            "Ingelsson E",
            "Abecasis G",
            "Chambers JC",
            "Kooner JS",
            "de Vries PS",
            "Morrison AC",
            "North KE",
            "Daviglus M",
            "Kraft P",
            "Martin NG",
            "Whitfield JB",
            "Abbas S",
            "Saleheen D",
            "Walters RG",
            "Holmes MV",
            "Black C",
            "Smith BH",
            "Justice AE",
            "Baras A",
            "Buring JE",
            "Ridker PM",
            "Chasman DI",
            "Kooperberg C",
            "Wei WQ",
            "Jarvik GP",
            "Namjou B",
            "Hayes MG",
            "Ritchie MD",
            "Jousilahti P",
            "Salomaa V",
            "Hveem K",
            "\u00c5svold BO",
            "Kubo M",
            "Kamatani Y",
            "Okada Y",
            "Murakami Y",
            "Thorsteinsdottir U",
            "Stefansson K",
            "Ho YL",
            "Lynch JA",
            "Rader DJ",
            "Tsao PS",
            "Chang KM",
            "Cho K",
            "O'Donnell CJ",
            "Gaziano JM",
            "Wilson P",
            "Rotimi CN",
            "Hazelhurst S",
            "Ramsay M",
            "Trembath RC",
            "van Heel DA",
            "Tamiya G",
            "Yamamoto M",
            "Kim BJ",
            "Mohlke KL",
            "Frayling TM",
            "Hirschhorn JN",
            "Kathiresan S",
            "Boehnke M",
            "Natarajan P",
            "Peloso GM",
            "Brown CD",
            "Morris AP",
            "Assimes TL",
            "Deloukas P",
            "Sun YV",
            "Willer CJ"
        ],
        "doi": "10.1038/s41586-021-04064-3",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "237",
        "volume": "600",
        "issue": "7890",
        "pages": "675-679",
        "pre": false,
        "pdate": "2021-12-11"
    },
    "10.1016/j.parkreldis.2021.03.028": {
        "title": "Task matters - challenging the motor system allows distinguishing unaffected Parkin mutation carriers from mutation-free controls.",
        "journal": "Parkinsonism & related disorders",
        "year": "2021",
        "abstract": "**Background**<br> Heterozygous carriers of *Parkin* mutations are suggested to be at risk of developing Parkinson's disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD in general, in particular regarding the prodromal phase. <br>**Objectives**<br> To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using a multimodal approach. <br>**Methods**<br> Twenty-seven healthy heterozygous Parkin mutation carriers (13 female. age: 48\u00a0\u00b1\u00a013 years) and 24 healthy non-mutation carriers (14 female. age: 48\u00a0\u00b1\u00a015 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were recalled based on their genetic profile and underwent a blinded assessment of motor and non-motor PD symptoms, transcranial sonography and sensor-based posturography and gait analyses under different conditions with increasing difficulty. For the latter, gradient-boosted trees were used to discriminate between carriers and non-carriers. The classification accuracy and the area under the curve of the receiver-operator characteristics curve were calculated. <br>**Results**<br> We observed no differences concerning motor or non-motor symptoms and substantia nigra hyperechogenicity. The best gradient-boosted trees-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification accuracy of up to 86%. The best-performing gradient-boosted trees-based model for gait analyses showed a balanced accuracy of up to 87% (dual-tasking). <br>**Conclusions**<br> Sensor-based quantification of movements allows to discriminate unaffected heterozygous mutation carriers from mutation-free controls. Thereby, it is crucial to challenge the motor system with more difficult tasks to unmask subtle motor alterations.",
        "authors": [
            "Prasuhn J",
            "Borsche M",
            "Hicks AA",
            "G\u00f6gele M",
            "Egger C",
            "Kritzinger C",
            "Pichler I",
            "Castelo-Rueda MP",
            "Langlott L",
            "Kasten M",
            "Mascalzoni D",
            "Klein C",
            "Pramstaller PP",
            "Br\u00fcggemann N"
        ],
        "doi": "10.1016/j.parkreldis.2021.03.028",
        "source_study": [
            "CHRIS PAREGEN"
        ],
        "ar": "225",
        "volume": "86",
        "issue": "",
        "pages": "101-104",
        "pre": false,
        "pdate": "2021-04-26"
    },
    "10.1111/joim.13242": {
        "title": "Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14\u00a0176 individuals.",
        "journal": "Journal of internal medicine",
        "year": "2021",
        "abstract": "**Background**<br> Mitochondria play an important role in cellular metabolism, and their dysfunction is postulated to be involved in metabolic disturbances. Mitochondrial DNA is present in multiple copies per cell. The quantification of mitochondrial DNA copy number (mtDNA-CN) might be used to assess mitochondrial dysfunction. <br>**Objectives**<br> We aimed to investigate the cross-sectional association of mtDNA-CN with type 2 diabetes and the potential mediating role of metabolic syndrome. <br>**Methods**<br> We examined 4812 patients from the German Chronic Kidney Disease (GCKD) study and 9364 individuals from the Cooperative Health Research in South Tyrol (CHRIS) study. MtDNA-CN was measured in whole blood using a plasmid-normalized qPCR-based assay. <br>**Results**<br> In both studies, mtDNA-CN showed a significant correlation with most metabolic syndrome parameters: mtDNA-CN decreased with increasing number of metabolic syndrome components. Furthermore, individuals with low mtDNA-CN had significantly higher odds of metabolic syndrome (OR\u00a0=\u00a01.025; 95% CI\u00a0=\u00a01.011-1.039, *P*\u00a0=\u00a03.19\u00a0\u00d7\u00a010<sup>-4</sup> , for each decrease of 10 mtDNA copies) and type 2 diabetes (OR\u00a0=\u00a01.027; 95% CI\u00a0=\u00a01.012-1.041; *P*\u00a0=\u00a02.84\u00a0\u00d7\u00a010<sup>-4</sup> ) in a model adjusted for age, sex, smoking and kidney function in the meta-analysis of both studies. Mediation analysis revealed that the association of mtDNA-CN with type 2 diabetes was mainly mediated by waist circumference in the GCKD study (66%) and by several metabolic syndrome parameters, especially body mass index and triglycerides, in the CHRIS study (41%). <br>**Conclusions**<br> Our data show an inverse association of mtDNA-CN with higher risk of metabolic syndrome and type 2 diabetes. A major part of the total effect of mtDNA-CN on type 2 diabetes is mediated by obesity parameters.",
        "authors": [
            "Fazzini F",
            "Lamina C",
            "Raftopoulou A",
            "Koller A",
            "Fuchsberger C",
            "Pattaro C",
            "Del Greco FM",
            "D\u00f6ttelmayer P",
            "Fendt L",
            "Fritz J",
            "Meiselbach H",
            "Sch\u00f6nherr S",
            "Forer L",
            "Weissensteiner H",
            "Pramstaller PP",
            "Eckardt KU",
            "Hicks AA",
            "Kronenberg F"
        ],
        "doi": "10.1111/joim.13242",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "222",
        "volume": "290",
        "issue": "1",
        "pages": "190-202",
        "pre": false,
        "pdate": "2021-01-17"
    },
    "10.1186/s12967-019-02130-z": {
        "title": "Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study.",
        "journal": "Journal of translational medicine",
        "year": "2019",
        "abstract": "**Background**<br> Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. <br>**Methods**<br> Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. <br>**Results**<br> We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8\u00a0kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9\u00a0kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean -\u20090.55, standard deviation, SD, 1.30) than non-T2D participants (mean -\u20091.30, SD,\u20091.17). <br>**Discussion**<br> Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.",
        "authors": [
            "Motta BM",
            "Grander C",
            "G\u00f6gele M",
            "Foco L",
            "Vukovic V",
            "Melotti R",
            "Fuchsberger C",
            "De Grandi A",
            "Cantaloni C",
            "Picard A",
            "Mascalzoni D",
            "Rossini A",
            "Pattaro C",
            "Tilg H",
            "Pramstaller PP"
        ],
        "doi": "10.1186/s12967-019-02130-z",
        "source_study": [
            "CHRIS NAFLD"
        ],
        "ar": "205",
        "volume": "17",
        "issue": "1",
        "pages": "408",
        "pre": false,
        "pdate": "2019-12-06"
    },
    "10.1038/s41467-020-15706-x": {
        "title": "Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.",
        "journal": "Nature communications",
        "year": "2020",
        "abstract": "The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N\u2009=\u2009293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.",
        "authors": [
            "Ntalla I",
            "Weng LC",
            "Cartwright JH",
            "Hall AW",
            "Sveinbjornsson G",
            "Tucker NR",
            "Choi SH",
            "Chaffin MD",
            "Roselli C",
            "Barnes MR",
            "Mifsud B",
            "Warren HR",
            "Hayward C",
            "Marten J",
            "Cranley JJ",
            "Concas MP",
            "Gasparini P",
            "Boutin T",
            "Kolcic I",
            "Polasek O",
            "Rudan I",
            "Araujo NM",
            "Lima-Costa MF",
            "Ribeiro ALP",
            "Souza RP",
            "Tarazona-Santos E",
            "Giedraitis V",
            "Ingelsson E",
            "Mahajan A",
            "Morris AP",
            "Del Greco M F",
            "Foco L",
            "G\u00f6gele M",
            "Hicks AA",
            "Cook JP",
            "Lind L",
            "Lindgren CM",
            "Sundstr\u00f6m J",
            "Nelson CP",
            "Riaz MB",
            "Samani NJ",
            "Sinagra G",
            "Ulivi S",
            "K\u00e4h\u00f6nen M",
            "Mishra PP",
            "Mononen N",
            "Nikus K",
            "Caulfield MJ",
            "Dominiczak A",
            "Padmanabhan S",
            "Montasser ME",
            "O'Connell JR",
            "Ryan K",
            "Shuldiner AR",
            "Aeschbacher S",
            "Conen D",
            "Risch L",
            "Th\u00e9riault S",
            "Hutri-K\u00e4h\u00f6nen N",
            "Lehtim\u00e4ki T",
            "Lyytik\u00e4inen LP",
            "Raitakari OT",
            "Barnes CLK",
            "Campbell H",
            "Joshi PK",
            "Wilson JF",
            "Isaacs A",
            "Kors JA",
            "van Duijn CM",
            "Huang PL",
            "Gudnason V",
            "Harris TB",
            "Launer LJ",
            "Smith AV",
            "Bottinger EP",
            "Loos RJF",
            "Nadkarni GN",
            "Preuss MH",
            "Correa A",
            "Mei H",
            "Wilson J",
            "Meitinger T",
            "M\u00fcller-Nurasyid M",
            "Peters A",
            "Waldenberger M",
            "Mangino M",
            "Spector TD",
            "Rienstra M",
            "van de Vegte YJ",
            "van der Harst P",
            "Verweij N",
            "K\u00e4\u00e4b S",
            "Schramm K",
            "Sinner MF",
            "Strauch K",
            "Cutler MJ",
            "Fatkin D",
            "London B",
            "Olesen M",
            "Roden DM",
            "Benjamin Shoemaker M",
            "Gustav Smith J",
            "Biggs ML",
            "Bis JC",
            "Brody JA",
            "Psaty BM",
            "Rice K",
            "Sotoodehnia N",
            "De Grandi A",
            "Fuchsberger C",
            "Pattaro C",
            "Pramstaller PP",
            "Ford I",
            "Wouter Jukema J",
            "Macfarlane PW",
            "Trompet S",
            "D\u00f6rr M",
            "Felix SB",
            "V\u00f6lker U",
            "Weiss S",
            "Havulinna AS",
            "Jula A",
            "S\u00e4\u00e4ksj\u00e4rvi K",
            "Salomaa V",
            "Guo X",
            "Heckbert SR",
            "Lin HJ",
            "Rotter JI",
            "Taylor KD",
            "Yao J",
            "de Mutsert R",
            "Maan AC",
            "Mook-Kanamori DO",
            "Noordam R",
            "Cucca F",
            "Ding J",
            "Lakatta EG",
            "Qian Y",
            "Tarasov KV",
            "Levy D",
            "Lin H",
            "Newton-Cheh CH",
            "Lunetta KL",
            "Murray AD",
            "Porteous DJ",
            "Smith BH",
            "Stricker BH",
            "Uitterlinden A",
            "van den Berg ME",
            "Haessler J",
            "Jackson RD",
            "Kooperberg C",
            "Peters U",
            "Reiner AP",
            "Whitsel EA",
            "Alonso A",
            "Arking DE",
            "Boerwinkle E",
            "Ehret GB",
            "Soliman EZ",
            "Avery CL",
            "Gogarten SM",
            "Kerr KF",
            "Laurie CC",
            "Seyerle AA",
            "Stilp A",
            "Assa S",
            "Abdullah Said M",
            "Yldau van der Ende M",
            "Lambiase PD",
            "Orini M",
            "Ramirez J",
            "Van Duijvenboden S",
            "Arnar DO",
            "Gudbjartsson DF",
            "Holm H",
            "Sulem P",
            "Thorleifsson G",
            "Thorolfsdottir RB",
            "Thorsteinsdottir U",
            "Benjamin EJ",
            "Tinker A",
            "Stefansson K",
            "Ellinor PT",
            "Jamshidi Y",
            "Lubitz SA",
            "Munroe PB"
        ],
        "doi": "10.1038/s41467-020-15706-x",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "200",
        "volume": "11",
        "issue": "1",
        "pages": "2542",
        "pre": false,
        "pdate": "2020-05-23"
    },
    "10.1172/jci.insight.131156": {
        "title": "KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.",
        "journal": "JCI insight",
        "year": "2019",
        "abstract": "**Background**<br> The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.<br>**Methods**<br> To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.<br>**Results**<br> We identified a genome-wide significant (*P* < 5 \u00d7 10<sup>-8</sup>) locus in the potassium voltage-gated channel subfamily D member 3 (*KCND3*) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the *KCND3* locus (OR 0.82 per minor T allele, *P* = 7.7 \u00d7 10<sup>-12</sup>) but did not reveal additional loci. Colocalization analyses indicate causal effects of *KCND3* gene expression levels on ERP in both cardiac left ventricle and tibial artery.<br>**Conclusions**<br> In this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the *KCND3* gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.",
        "authors": [
            "Teumer A",
            "Trenkwalder T",
            "Kessler T",
            "Jamshidi Y",
            "van den Berg ME",
            "Kaess B",
            "Nelson CP",
            "Bastiaenen R",
            "De Bortoli M",
            "Rossini A",
            "Deisenhofer I",
            "Stark K",
            "Assa S",
            "Braund PS",
            "Cabrera C",
            "Dominiczak AF",
            "G\u00f6gele M",
            "Hall LM",
            "Ikram MA",
            "Kavousi M",
            "Lackner KJ",
            "M\u00fcller C",
            "M\u00fcnzel T",
            "Nauck M",
            "Padmanabhan S",
            "Pfeiffer N",
            "Spector TD",
            "Uitterlinden AG",
            "Verweij N",
            "V\u00f6lker U",
            "Warren HR",
            "Zafar M",
            "Felix SB",
            "Kors JA",
            "Snieder H",
            "Munroe PB",
            "Pattaro C",
            "Fuchsberger C",
            "Schmidt G",
            "Nolte IM",
            "Schunkert H",
            "Pramstaller PP",
            "Wild PS",
            "van der Harst P",
            "Stricker BH",
            "Schnabel RB",
            "Samani NJ",
            "Hengstenberg C",
            "D\u00f6rr M",
            "Behr ER",
            "Reinhard W"
        ],
        "doi": "10.1172/jci.insight.131156",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "182",
        "volume": "4",
        "issue": "23",
        "pages": "",
        "pre": false,
        "pdate": "2019-10-11"
    },
    "10.1038/s41588-019-0504-x": {
        "title": "Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.",
        "journal": "Nature genetics",
        "year": "2019",
        "abstract": "Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, *HNF1A* and *HNF4A*. Experimental validation showed that HNF4A transactivated the promoter of *ABCG2*, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.",
        "authors": [
            "Tin A",
            "Marten J",
            "Halperin Kuhns VL",
            "Li Y",
            "Wuttke M",
            "Kirsten H",
            "Sieber KB",
            "Qiu C",
            "Gorski M",
            "Yu Z",
            "Giri A",
            "Sveinbjornsson G",
            "Li M",
            "Chu AY",
            "Hoppmann A",
            "O'Connor LJ",
            "Prins B",
            "Nutile T",
            "Noce D",
            "Akiyama M",
            "Cocca M",
            "Ghasemi S",
            "van der Most PJ",
            "Horn K",
            "Xu Y",
            "Fuchsberger C",
            "Sedaghat S",
            "Afaq S",
            "Amin N",
            "\u00c4rnl\u00f6v J",
            "Bakker SJL",
            "Bansal N",
            "Baptista D",
            "Bergmann S",
            "Biggs ML",
            "Biino G",
            "Boerwinkle E",
            "Bottinger EP",
            "Boutin TS",
            "Brumat M",
            "Burkhardt R",
            "Campana E",
            "Campbell A",
            "Campbell H",
            "Carroll RJ",
            "Catamo E",
            "Chambers JC",
            "Ciullo M",
            "Concas MP",
            "Coresh J",
            "Corre T",
            "Cusi D",
            "Felicita SC",
            "de Borst MH",
            "De Grandi A",
            "de Mutsert R",
            "de Vries APJ",
            "Delgado G",
            "Demirkan A",
            "Devuyst O",
            "Dittrich K",
            "Eckardt KU",
            "Ehret G",
            "Endlich K",
            "Evans MK",
            "Gansevoort RT",
            "Gasparini P",
            "Giedraitis V",
            "Gieger C",
            "Girotto G",
            "G\u00f6gele M",
            "Gordon SD",
            "Gudbjartsson DF",
            "Gudnason V",
            "Haller T",
            "Hamet P",
            "Harris TB",
            "Hayward C",
            "Hicks AA",
            "Hofer E",
            "Holm H",
            "Huang W",
            "Hutri-K\u00e4h\u00f6nen N",
            "Hwang SJ",
            "Ikram MA",
            "Lewis RM",
            "Ingelsson E",
            "Jakobsdottir J",
            "Jonsdottir I",
            "Jonsson H",
            "Joshi PK",
            "Josyula NS",
            "Jung B",
            "K\u00e4h\u00f6nen M",
            "Kamatani Y",
            "Kanai M",
            "Kerr SM",
            "Kiess W",
            "Kleber ME",
            "Koenig W",
            "Kooner JS",
            "K\u00f6rner A",
            "Kovacs P",
            "Kr\u00e4mer BK",
            "Kronenberg F",
            "Kubo M",
            "K\u00fchnel B",
            "La Bianca M",
            "Lange LA",
            "Lehne B",
            "Lehtim\u00e4ki T",
            "Liu J",
            "Loeffler M",
            "Loos RJF",
            "Lyytik\u00e4inen LP",
            "Magi R",
            "Mahajan A",
            "Martin NG",
            "M\u00e4rz W",
            "Mascalzoni D",
            "Matsuda K",
            "Meisinger C",
            "Meitinger T",
            "Metspalu A",
            "Milaneschi Y",
            "O'Donnell CJ",
            "Wilson OD",
            "Gaziano JM",
            "Mishra PP",
            "Mohlke KL",
            "Mononen N",
            "Montgomery GW",
            "Mook-Kanamori DO",
            "M\u00fcller-Nurasyid M",
            "Nadkarni GN",
            "Nalls MA",
            "Nauck M",
            "Nikus K",
            "Ning B",
            "Nolte IM",
            "Noordam R",
            "O'Connell JR",
            "Olafsson I",
            "Padmanabhan S",
            "Penninx BWJH",
            "Perls T",
            "Peters A",
            "Pirastu M",
            "Pirastu N",
            "Pistis G",
            "Polasek O",
            "Ponte B",
            "Porteous DJ",
            "Poulain T",
            "Preuss MH",
            "Rabelink TJ",
            "Raffield LM",
            "Raitakari OT",
            "Rettig R",
            "Rheinberger M",
            "Rice KM",
            "Rizzi F",
            "Robino A",
            "Rudan I",
            "Krajcoviechova A",
            "Cifkova R",
            "Rueedi R",
            "Ruggiero D",
            "Ryan KA",
            "Saba Y",
            "Salvi E",
            "Schmidt H",
            "Schmidt R",
            "Shaffer CM",
            "Smith AV",
            "Smith BH",
            "Spracklen CN",
            "Strauch K",
            "Stumvoll M",
            "Sulem P",
            "Tajuddin SM",
            "Teren A",
            "Thiery J",
            "Thio CHL",
            "Thorsteinsdottir U",
            "Toniolo D",
            "T\u00f6njes A",
            "Tremblay J",
            "Uitterlinden AG",
            "Vaccargiu S",
            "van der Harst P",
            "van Duijn CM",
            "Verweij N",
            "V\u00f6lker U",
            "Vollenweider P",
            "Waeber G",
            "Waldenberger M",
            "Whitfield JB",
            "Wild SH",
            "Wilson JF",
            "Yang Q",
            "Zhang W",
            "Zonderman AB",
            "Bochud M",
            "Wilson JG",
            "Pendergrass SA",
            "Ho K",
            "Parsa A",
            "Pramstaller PP",
            "Psaty BM",
            "B\u00f6ger CA",
            "Snieder H",
            "Butterworth AS",
            "Okada Y",
            "Edwards TL",
            "Stefansson K",
            "Susztak K",
            "Scholz M",
            "Heid IM",
            "Hung AM",
            "Teumer A",
            "Pattaro C",
            "Woodward OM",
            "Vitart V",
            "K\u00f6ttgen A"
        ],
        "doi": "10.1038/s41588-019-0504-x",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "170",
        "volume": "51",
        "issue": "10",
        "pages": "1459-1474",
        "pre": false,
        "pdate": "2019-10-04"
    },
    "10.1161/CIRCGEN.118.002384": {
        "title": "Lipidomics, Atrial Conduction, and Body Mass Index.",
        "journal": "Circulation. Genomic and precision medicine",
        "year": "2019",
        "abstract": "**Background**<br>Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. <br>**Methods**<br> To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734\u2009481), and genetic association analysis of PWD in 5 population-based studies (n=24\u2009236). <br>**Results**<br> We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; *P*=1.1\u00d710<sup>-4</sup>) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD (*P*=8.3\u00d710<sup>-5</sup>) and %PC 38:3 ( *P*=0.014). <br>**Conclusions**<br> Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity.",
        "authors": [
            "Del Greco M F",
            "Foco L",
            "Teumer A",
            "Verweij N",
            "Paglia G",
            "Meraviglia V",
            "Melotti R",
            "Vukovic V",
            "Rauhe W",
            "Joshi PK",
            "Demirkan A",
            "Felix SB",
            "Pietzner M",
            "Said MA",
            "van de Vegte YJ",
            "van der Harst P",
            "Wright AF",
            "Hicks AA",
            "Campbell H",
            "D\u00f6rr M",
            "Snieder H",
            "Wilson JF",
            "Pramstaller PP",
            "Rossini A",
            "Pattaro C"
        ],
        "doi": "10.1161/CIRCGEN.118.002384",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "161",
        "volume": "12",
        "issue": "7",
        "pages": "e002384",
        "pre": false,
        "pdate": "2019-07-16"
    },
    "10.1038/s41467-019-11576-0": {
        "title": "Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.",
        "journal": "Nature communications",
        "year": "2019",
        "abstract": "Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n\u2009=\u2009564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n\u2009=\u2009192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including *TGFB1*, *MUC1*, *PRKCI*, and *OAF*), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of *OAF* and *PRKCI* orthologs in *Drosophila* nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.",
        "authors": [
            "Teumer A",
            "Li Y",
            "Ghasemi S",
            "Prins BP",
            "Wuttke M",
            "Hermle T",
            "Giri A",
            "Sieber KB",
            "Qiu C",
            "Kirsten H",
            "Tin A",
            "Chu AY",
            "Bansal N",
            "Feitosa MF",
            "Wang L",
            "Chai JF",
            "Cocca M",
            "Fuchsberger C",
            "Gorski M",
            "Hoppmann A",
            "Horn K",
            "Li M",
            "Marten J",
            "Noce D",
            "Nutile T",
            "Sedaghat S",
            "Sveinbjornsson G",
            "Tayo BO",
            "van der Most PJ",
            "Xu Y",
            "Yu Z",
            "Gerstner L",
            "\u00c4rnl\u00f6v J",
            "Bakker SJL",
            "Baptista D",
            "Biggs ML",
            "Boerwinkle E",
            "Brenner H",
            "Burkhardt R",
            "Carroll RJ",
            "Chee ML",
            "Chee ML",
            "Chen M",
            "Cheng CY",
            "Cook JP",
            "Coresh J",
            "Corre T",
            "Danesh J",
            "de Borst MH",
            "De Grandi A",
            "de Mutsert R",
            "de Vries APJ",
            "Degenhardt F",
            "Dittrich K",
            "Divers J",
            "Eckardt KU",
            "Ehret G",
            "Endlich K",
            "Felix JF",
            "Franco OH",
            "Franke A",
            "Freedman BI",
            "Freitag-Wolf S",
            "Gansevoort RT",
            "Giedraitis V",
            "G\u00f6gele M",
            "Grundner-Culemann F",
            "Gudbjartsson DF",
            "Gudnason V",
            "Hamet P",
            "Harris TB",
            "Hicks AA",
            "Holm H",
            "Foo VHX",
            "Hwang SJ",
            "Ikram MA",
            "Ingelsson E",
            "Jaddoe VWV",
            "Jakobsdottir J",
            "Josyula NS",
            "Jung B",
            "K\u00e4h\u00f6nen M",
            "Khor CC",
            "Kiess W",
            "Koenig W",
            "K\u00f6rner A",
            "Kovacs P",
            "Kramer H",
            "Kr\u00e4mer BK",
            "Kronenberg F",
            "Lange LA",
            "Langefeld CD",
            "Lee JJ",
            "Lehtim\u00e4ki T",
            "Lieb W",
            "Lim SC",
            "Lind L",
            "Lindgren CM",
            "Liu J",
            "Loeffler M",
            "Lyytik\u00e4inen LP",
            "Mahajan A",
            "Maranville JC",
            "Mascalzoni D",
            "McMullen B",
            "Meisinger C",
            "Meitinger T",
            "Miliku K",
            "Mook-Kanamori DO",
            "M\u00fcller-Nurasyid M",
            "Mychaleckyj JC",
            "Nauck M",
            "Nikus K",
            "Ning B",
            "Noordam R",
            "Connell JO",
            "Olafsson I",
            "Palmer ND",
            "Peters A",
            "Podgornaia AI",
            "Ponte B",
            "Poulain T",
            "Pramstaller PP",
            "Rabelink TJ",
            "Raffield LM",
            "Reilly DF",
            "Rettig R",
            "Rheinberger M",
            "Rice KM",
            "Rivadeneira F",
            "Runz H",
            "Ryan KA",
            "Sabanayagam C",
            "Saum KU",
            "Sch\u00f6ttker B",
            "Shaffer CM",
            "Shi Y",
            "Smith AV",
            "Strauch K",
            "Stumvoll M",
            "Sun BB",
            "Szymczak S",
            "Tai ES",
            "Tan NYQ",
            "Taylor KD",
            "Teren A",
            "Tham YC",
            "Thiery J",
            "Thio CHL",
            "Thomsen H",
            "Thorsteinsdottir U",
            "T\u00f6njes A",
            "Tremblay J",
            "Uitterlinden AG",
            "van der Harst P",
            "Verweij N",
            "Vogelezang S",
            "V\u00f6lker U",
            "Waldenberger M",
            "Wang C",
            "Wilson OD",
            "Wong C",
            "Wong TY",
            "Yang Q",
            "Yasuda M",
            "Akilesh S",
            "Bochud M",
            "B\u00f6ger CA",
            "Devuyst O",
            "Edwards TL",
            "Ho K",
            "Morris AP",
            "Parsa A",
            "Pendergrass SA",
            "Psaty BM",
            "Rotter JI",
            "Stefansson K",
            "Wilson JG",
            "Susztak K",
            "Snieder H",
            "Heid IM",
            "Scholz M",
            "Butterworth AS",
            "Hung AM",
            "Pattaro C",
            "K\u00f6ttgen A"
        ],
        "doi": "10.1038/s41467-019-11576-0",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "160",
        "volume": "10",
        "issue": "1",
        "pages": "4130",
        "pre": false,
        "pdate": "2019-09-13"
    },
    "10.1038/s41588-019-0407-x": {
        "title": "A catalog of genetic loci associated with kidney function from analyses of a million individuals.",
        "journal": "Nature genetics",
        "year": "2019",
        "abstract": "Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n\u2009=\u20091,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n\u2009=\u2009416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.",
        "authors": [
            "Wuttke M",
            "Li Y",
            "Li M",
            "Sieber KB",
            "Feitosa MF",
            "Gorski M",
            "Tin A",
            "Wang L",
            "Chu AY",
            "Hoppmann A",
            "Kirsten H",
            "Giri A",
            "Chai JF",
            "Sveinbjornsson G",
            "Tayo BO",
            "Nutile T",
            "Fuchsberger C",
            "Marten J",
            "Cocca M",
            "Ghasemi S",
            "Xu Y",
            "Horn K",
            "Noce D",
            "van der Most PJ",
            "Sedaghat S",
            "Yu Z",
            "Akiyama M",
            "Afaq S",
            "Ahluwalia TS",
            "Almgren P",
            "Amin N",
            "\u00c4rnl\u00f6v J",
            "Bakker SJL",
            "Bansal N",
            "Baptista D",
            "Bergmann S",
            "Biggs ML",
            "Biino G",
            "Boehnke M",
            "Boerwinkle E",
            "Boissel M",
            "Bottinger EP",
            "Boutin TS",
            "Brenner H",
            "Brumat M",
            "Burkhardt R",
            "Butterworth AS",
            "Campana E",
            "Campbell A",
            "Campbell H",
            "Canouil M",
            "Carroll RJ",
            "Catamo E",
            "Chambers JC",
            "Chee ML",
            "Chee ML",
            "Chen X",
            "Cheng CY",
            "Cheng Y",
            "Christensen K",
            "Cifkova R",
            "Ciullo M",
            "Concas MP",
            "Cook JP",
            "Coresh J",
            "Corre T",
            "Sala CF",
            "Cusi D",
            "Danesh J",
            "Daw EW",
            "de Borst MH",
            "De Grandi A",
            "de Mutsert R",
            "de Vries APJ",
            "Degenhardt F",
            "Delgado G",
            "Demirkan A",
            "Di Angelantonio E",
            "Dittrich K",
            "Divers J",
            "Dorajoo R",
            "Eckardt KU",
            "Ehret G",
            "Elliott P",
            "Endlich K",
            "Evans MK",
            "Felix JF",
            "Foo VHX",
            "Franco OH",
            "Franke A",
            "Freedman BI",
            "Freitag-Wolf S",
            "Friedlander Y",
            "Froguel P",
            "Gansevoort RT",
            "Gao H",
            "Gasparini P",
            "Gaziano JM",
            "Giedraitis V",
            "Gieger C",
            "Girotto G",
            "Giulianini F",
            "G\u00f6gele M",
            "Gordon SD",
            "Gudbjartsson DF",
            "Gudnason V",
            "Haller T",
            "Hamet P",
            "Harris TB",
            "Hartman CA",
            "Hayward C",
            "Hellwege JN",
            "Heng CK",
            "Hicks AA",
            "Hofer E",
            "Huang W",
            "Hutri-K\u00e4h\u00f6nen N",
            "Hwang SJ",
            "Ikram MA",
            "Indridason OS",
            "Ingelsson E",
            "Ising M",
            "Jaddoe VWV",
            "Jakobsdottir J",
            "Jonas JB",
            "Joshi PK",
            "Josyula NS",
            "Jung B",
            "K\u00e4h\u00f6nen M",
            "Kamatani Y",
            "Kammerer CM",
            "Kanai M",
            "Kastarinen M",
            "Kerr SM",
            "Khor CC",
            "Kiess W",
            "Kleber ME",
            "Koenig W",
            "Kooner JS",
            "K\u00f6rner A",
            "Kovacs P",
            "Kraja AT",
            "Krajcoviechova A",
            "Kramer H",
            "Kr\u00e4mer BK",
            "Kronenberg F",
            "Kubo M",
            "K\u00fchnel B",
            "Kuokkanen M",
            "Kuusisto J",
            "La Bianca M",
            "Laakso M",
            "Lange LA",
            "Langefeld CD",
            "Lee JJ",
            "Lehne B",
            "Lehtim\u00e4ki T",
            "Lieb W",
            "Lim SC",
            "Lind L",
            "Lindgren CM",
            "Liu J",
            "Liu J",
            "Loeffler M",
            "Loos RJF",
            "Lucae S",
            "Lukas MA",
            "Lyytik\u00e4inen LP",
            "M\u00e4gi R",
            "Magnusson PKE",
            "Mahajan A",
            "Martin NG",
            "Martins J",
            "M\u00e4rz W",
            "Mascalzoni D",
            "Matsuda K",
            "Meisinger C",
            "Meitinger T",
            "Melander O",
            "Metspalu A",
            "Mikaelsdottir EK",
            "Milaneschi Y",
            "Miliku K",
            "Mishra PP",
            "Mohlke KL",
            "Mononen N",
            "Montgomery GW",
            "Mook-Kanamori DO",
            "Mychaleckyj JC",
            "Nadkarni GN",
            "Nalls MA",
            "Nauck M",
            "Nikus K",
            "Ning B",
            "Nolte IM",
            "Noordam R",
            "O'Connell J",
            "O'Donoghue ML",
            "Olafsson I",
            "Oldehinkel AJ",
            "Orho-Melander M",
            "Ouwehand WH",
            "Padmanabhan S",
            "Palmer ND",
            "Palsson R",
            "Penninx BWJH",
            "Perls T",
            "Perola M",
            "Pirastu M",
            "Pirastu N",
            "Pistis G",
            "Podgornaia AI",
            "Polasek O",
            "Ponte B",
            "Porteous DJ",
            "Poulain T",
            "Pramstaller PP",
            "Preuss MH",
            "Prins BP",
            "Province MA",
            "Rabelink TJ",
            "Raffield LM",
            "Raitakari OT",
            "Reilly DF",
            "Rettig R",
            "Rheinberger M",
            "Rice KM",
            "Ridker PM",
            "Rivadeneira F",
            "Rizzi F",
            "Roberts DJ",
            "Robino A",
            "Rossing P",
            "Rudan I",
            "Rueedi R",
            "Ruggiero D",
            "Ryan KA",
            "Saba Y",
            "Sabanayagam C",
            "Salomaa V",
            "Salvi E",
            "Saum KU",
            "Schmidt H",
            "Schmidt R",
            "Sch\u00f6ttker B",
            "Schulz CA",
            "Schupf N",
            "Shaffer CM",
            "Shi Y",
            "Smith AV",
            "Smith BH",
            "Soranzo N",
            "Spracklen CN",
            "Strauch K",
            "Stringham HM",
            "Stumvoll M",
            "Svensson PO",
            "Szymczak S",
            "Tai ES",
            "Tajuddin SM",
            "Tan NYQ",
            "Taylor KD",
            "Teren A",
            "Tham YC",
            "Thiery J",
            "Thio CHL",
            "Thomsen H",
            "Thorleifsson G",
            "Toniolo D",
            "T\u00f6njes A",
            "Tremblay J",
            "Tzoulaki I",
            "Uitterlinden AG",
            "Vaccargiu S",
            "van Dam RM",
            "van der Harst P",
            "van Duijn CM",
            "Velez Edward DR",
            "Verweij N",
            "Vogelezang S",
            "V\u00f6lker U",
            "Vollenweider P",
            "Waeber G",
            "Waldenberger M",
            "Wallentin L",
            "Wang YX",
            "Wang C",
            "Waterworth DM",
            "Bin Wei W",
            "White H",
            "Whitfield JB",
            "Wild SH",
            "Wilson JF",
            "Wojczynski MK",
            "Wong C",
            "Wong TY",
            "Xu L",
            "Yang Q",
            "Yasuda M",
            "Yerges-Armstrong LM",
            "Zhang W",
            "Zonderman AB",
            "Rotter JI",
            "Bochud M",
            "Psaty BM",
            "Vitart V",
            "Wilson JG",
            "Dehghan A",
            "Parsa A",
            "Chasman DI",
            "Ho K",
            "Morris AP",
            "Devuyst O",
            "Akilesh S",
            "Pendergrass SA",
            "Sim X",
            "B\u00f6ger CA",
            "Okada Y",
            "Edwards TL",
            "Snieder H",
            "Stefansson K",
            "Hung AM",
            "Heid IM",
            "Scholz M",
            "Teumer A",
            "K\u00f6ttgen A",
            "Pattaro C"
        ],
        "doi": "10.1038/s41588-019-0407-x",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "155",
        "volume": "51",
        "issue": "6",
        "pages": "957-972",
        "pre": false,
        "pdate": "2019-06-04"
    },
    "10.1016/j.jacc.2019.03.519": {
        "title": "Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.",
        "journal": "Journal of the American College of Cardiology",
        "year": "2019",
        "abstract": "**Background**<br>Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in\u00a0vitro models and observations in patients with severe medical conditions. <br>**Objectives**<br> This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. <br>**Methods**<br> Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 \u00b1 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. <br>**Results**<br> Lower calcium was associated with longer QT intervals (-11.5\u00a0ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2\u00a0ms; 99.75%\u00a0CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8\u00a0ms; 99.75%\u00a0CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. <br>**Conclusions**<br>The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5\u00a0ms.",
        "authors": [
            "Noordam R",
            "Young WJ",
            "Salman R",
            "Kanters JK",
            "van den Berg ME",
            "van Heemst D",
            "Lin HJ",
            "Barreto SM",
            "Biggs ML",
            "Biino G",
            "Catamo E",
            "Concas MP",
            "Ding J",
            "Evans DS",
            "Foco L",
            "Grarup N",
            "Lyytik\u00e4inen LP",
            "Mangino M",
            "Mei H",
            "van der Most PJ",
            "M\u00fcller-Nurasyid M",
            "Nelson CP",
            "Qian Y",
            "Repetto L",
            "Said MA",
            "Shah N",
            "Schramm K",
            "Vidigal PG",
            "Weiss S",
            "Yao J",
            "Zilhao NR",
            "Brody JA",
            "Braund PS",
            "Brumat M",
            "Campana E",
            "Christofidou P",
            "Caulfield MJ",
            "De Grandi A",
            "Dominiczak AF",
            "Doney ASF",
            "Eiriksdottir G",
            "Ellervik C",
            "Giatti L",
            "G\u00f6gele M",
            "Graff C",
            "Guo X",
            "van der Harst P",
            "Joshi PK",
            "K\u00e4h\u00f6nen M",
            "Kestenbaum B",
            "Lima-Costa MF",
            "Linneberg A",
            "Maan AC",
            "Meitinger T",
            "Padmanabhan S",
            "Pattaro C",
            "Peters A",
            "Petersmann A",
            "Sever P",
            "Sinner MF",
            "Shen X",
            "Stanton A",
            "Strauch K",
            "Soliman EZ",
            "Tarasov KV",
            "Taylor KD",
            "Thio CHL",
            "Uitterlinden AG",
            "Vaccargiu S",
            "Waldenberger M",
            "Robino A",
            "Correa A",
            "Cucca F",
            "Cummings SR",
            "D\u00f6rr M",
            "Girotto G",
            "Gudnason V",
            "Hansen T",
            "Heckbert SR",
            "Juhl CR",
            "K\u00e4\u00e4b S",
            "Lehtim\u00e4ki T",
            "Liu Y",
            "Lotufo PA",
            "Palmer CNA",
            "Pirastu M",
            "Pramstaller PP",
            "Ribeiro ALP",
            "Rotter JI",
            "Samani NJ",
            "Snieder H",
            "Spector TD",
            "Stricker BH",
            "Verweij N",
            "Wilson JF",
            "Wilson JG",
            "Jukema JW",
            "Tinker A",
            "Newton-Cheh CH",
            "Sotoodehnia N",
            "Mook-Kanamori DO",
            "Munroe PB",
            "Warren HR"
        ],
        "doi": "10.1016/j.jacc.2019.03.519",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "154",
        "volume": "73",
        "issue": "24",
        "pages": "3118-3131",
        "pre": false,
        "pdate": "2019-06-22"
    },
    "10.1371/journal.pone.0215053": {
        "title": "Effects of smoking status, history and intensity on heart rate variability in the general population: The CHRIS study.",
        "journal": "PloS one",
        "year": "2019",
        "abstract": "**Background**<br>Heart rate variability (HRV) reflects the autonomous nervous system modulation on heart rate and is associated with several pathologies, including cardiac mortality. While mechanistic studies show that smoking is associated with lower HRV, population-based studies present conflicting results. <br>**Methods**<br> We assessed the mutual effects of active smoking status, cumulative smoking history, and current smoking intensity, on HRV among 4751 adults from the Cooperative Health Research In South Tyrol (CHRIS) study. The HRV metrics standard deviation of normal-to-normal (NN) inter-beat intervals (SDNN), square root of the mean squared differences of consecutive NN intervals (RMSSD), total power (TP), low (LF) and high frequency (HF) power, and their ratio (LF/HF), were derived from 20-minute electrocardiograms. Smoking status, pack-years (PY), and tobacco grams/day from standardized questionnaires were the main exposures. We fitted linear mixed models to account for relatedness, non-linearity, and moderating effects, and including fractional polynomials. <br>**Results**<br> Past smokers had higher HRV levels than never smokers, independently of PY. The association of HRV with current smoking became apparent when accounting for the interaction between smoking status and PY. In current smokers, but not in past smokers, we observed HRV reductions between 2.0% (SDNN) and 4.9% (TP) every 5 PY increase. Furthermore, current smokers were characterized by dose-response reductions of 9.8% (SDNN), 8.9% (RMSSD), 20.1% (TP), 17.7% (LF), and 19.1% (HF), respectively, every 10 grams/day of smoked tobacco, independently of common cardiometabolic conditions and HRV-modifying drugs. The LF/HF ratio was not associated with smoking status, history, or intensity. <br>**Conclusions**<br> Smoking cessation was associated with higher HRV levels. In current smokers, heavier smoking intensity appears gradually detrimental on HRV, corroborating previous evidence. By affecting both the sympathetic and parasympathetic nervous system indexes, but not the LF/HF balance, smoking intensity seems to exert a systemic dysautonomic effect.",
        "authors": [
            "Murgia F",
            "Melotti R",
            "Foco L",
            "G\u00f6gele M",
            "Meraviglia V",
            "Motta B",
            "Steger A",
            "Toifl M",
            "Sinnecker D",
            "M\u00fcller A",
            "Merati G",
            "Schmidt G",
            "Rossini A",
            "Pramstaller PP",
            "Pattaro C"
        ],
        "doi": "10.1371/journal.pone.0215053",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "152",
        "volume": "14",
        "issue": "4",
        "pages": "e0215053",
        "pre": false,
        "pdate": "2019-04-10"
    },
    "10.1093/bioinformatics/bty541": {
        "title": "Comparative assessment of different familial aggregation methods in the context of large and unstructured pedigrees.",
        "journal": "Bioinformatics",
        "year": "2019",
        "abstract": "**Motivation**<br> Familial aggregation analysis is an important early step for characterizing the genetic determinants of phenotypes in epidemiological studies. To facilitate this analysis, a collection of methods to detect familial aggregation in large pedigrees has been made available recently. However, efficacy of these methods in real world scenarios remains largely unknown. Here, we assess the performance of five aggregation methods to identify individuals or groups of related individuals affected by a Mendelian trait within a large set of decoys. We investigate method performance under a representative set of combinations of causal variant penetrance, trait prevalence and number of affected generations in the pedigree. These methods are then applied to assess familial aggregation of familial hypercholesterolemia and stroke, in the context of the Cooperative Health Research in South Tyrol (CHRIS) study. <br>**Results**<br> We find that in some situations statistical hypothesis testing with a binomial null distribution achieves performance similar to methods that are based on kinship information, while kinship based methods perform better when information is available on fewer generations. Potential case families from the CHRIS study are reported and the results are discussed taking into account insights from the performance assessment. <br>**Availability and implementation**<br> The familial aggregation analysis package is freely available at the Bioconductor repository, [http://www.bioconductor.org/packages/FamAgg](http://www.bioconductor.org/packages/FamAgg). <br>**Supplementary information**<br> Supplementary data are available at [Bioinformatics online](https://doi.org/10.1093/bioinformatics/bty541).",
        "authors": [
            "Weichenberger CX",
            "Rainer J",
            "Pattaro C",
            "Pramstaller PP",
            "Domingues FS"
        ],
        "doi": "10.1093/bioinformatics/bty541",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "148",
        "volume": "35",
        "issue": "1",
        "pages": "69-76",
        "pre": false,
        "pdate": "2018-07-17"
    },
    "10.1016/j.cca.2018.08.014": {
        "title": "Influence of collection tubes during quantitative targeted metabolomics studies in human blood samples.",
        "journal": "Clinica chimica acta",
        "year": "2018",
        "abstract": "**Background**<br> Plasma and serum are the most widely used matrices in clinical studies. However, some variability in absolute concentrations of metabolites are likely to be observed in these collection tubes matrices. <br>**Methods**<br> We analyzed 189 metabolites using the same protocol for quantitative targeted metabolomics (LC-MS/MS AbsoluteIDQ p180 Kit Biocrates) in three types of samples, serum, plasma EDTA and citrate, of 80 subjects from the Cooperative Health Research In South Tyrol cohort (40 healthy elderly and 40 healthy young). <br>**Results**<br> The concentration levels were higher in serum than citrate and EDTA, in particular for amino acids and biogenic amines. The average Pearson's correlation coefficients were however always higher than 0.7 for these two classes of metabolites. We could also demonstrate that blank EDTA vacutainer tubes contain a significant amount of sarcosine. Finally, we compared the metabolome of young people against elderly subjects and found that the highest number of metabolites significantly changing with age was detected in serum. <br>**Conclusions**<br> Serum samples provide higher sensitivity for biomarker discovery studies. Due to the presence of spurious amount of sarcosine in vacutainer EDTA tubes, plasma EDTA is not suitable for studies requiring accurate quantification of sarcosine.",
        "authors": [
            "Paglia G",
            "Del Greco FM",
            "Sigurdsson BB",
            "Rainer J",
            "Volani C",
            "Hicks AA",
            "Pramstaller PP",
            "Smarason SV"
        ],
        "doi": "10.1016/j.cca.2018.08.014",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "142",
        "volume": "486",
        "issue": "",
        "pages": "320-328",
        "pre": false,
        "pdate": "2018-08-17"
    },
    "10.1016/j.jpain.2018.06.007": {
        "title": "Structural Consistency of the Pain Sensitivity Questionnaire in the Cooperative Health Research In South Tyrol (CHRIS) Population-Based Study.",
        "journal": "The journal of pain",
        "year": "2018",
        "abstract": "The self-reported Pain Sensitivity Questionnaire (PSQ) is a valid supplement to experimental pain testing. However, the latent constructs determining the originally proposed 1 general score (PSQ-total) and 2 subscores (PSQ-moderate and PSQ-minor) have not been consistently investigated in population-based studies or between genders. Based on a single construct hypothesized by expert knowledge or alternative constructs upon empirical evidence, PSQ structures were explored and confirmed among 4,820 participants aged 18 to 93 years of the Cooperative Health Research In South Tyrol (CHRIS) study. By exploratory factor analysis, we identified 3 alternative sets of PSQ imagined painful situations comprising 14, 10, and 9 items, which displayed simple structures of the rotated factor loadings of direct interpretation. In confirmatory analysis (CFA) of 1 latent factor, the 10-item set yielded acceptable goodness-of-fit overall, better fit than the alternative sets and consistent structural properties between genders. Separate analyses based on 14- and 9-item sets returned considerable correlations between 2 latent constructs. In higher-order CFA with each set, 1 first-order general factor explained a large part of the variances of 2 second-order factors. One dominant construct consistently describes the factorial structure of the PSQ. Averaging across the 10-item set, the PSQ-short score represents a structurally robust, gender-consistent, and practical measure of general pain sensitivity. <br>**Perspective**<br> One dominant latent construct of general pain sensitivity consistently determines responses to the self-reported PSQ. The PSQ-short score maintains similar psychometric properties to the PSQ-total and between genders. This measure is attractive for large-scale research and clinical screening of pain sensitivity.",
        "authors": [
            "Melotti R",
            "Ruscheweyh R",
            "Pramstaller PP",
            "Hicks AA",
            "Pattaro C"
        ],
        "doi": "10.1016/j.jpain.2018.06.007",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "126",
        "volume": "19",
        "issue": "12",
        "pages": "1424-1434",
        "pre": false,
        "pdate": "2018-07-19"
    },
    "10.1038/s41467-018-06356-1": {
        "title": "Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.",
        "journal": "Nature communications",
        "year": "2018",
        "abstract": "Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.",
        "authors": [
            "Teumer A",
            "Chaker L",
            "Groeneweg S",
            "Li Y",
            "Di Munno C",
            "Barbieri C",
            "Schultheiss UT",
            "Traglia M",
            "Ahluwalia TS",
            "Akiyama M",
            "Appel EVR",
            "Arking DE",
            "Arnold A",
            "Astrup A",
            "Beekman M",
            "Beilby JP",
            "Bekaert S",
            "Boerwinkle E",
            "Brown SJ",
            "De Buyzere M",
            "Campbell PJ",
            "Ceresini G",
            "Cerqueira C",
            "Cucca F",
            "Deary IJ",
            "Deelen J",
            "Eckardt KU",
            "Ekici AB",
            "Eriksson JG",
            "Ferrrucci L",
            "Fiers T",
            "Fiorillo E",
            "Ford I",
            "Fox CS",
            "Fuchsberger C",
            "Galesloot TE",
            "Gieger C",
            "G\u00f6gele M",
            "De Grandi A",
            "Grarup N",
            "Greiser KH",
            "Haljas K",
            "Hansen T",
            "Harris SE",
            "van Heemst D",
            "den Heijer M",
            "Hicks AA",
            "den Hollander W",
            "Homuth G",
            "Hui J",
            "Ikram MA",
            "Ittermann T",
            "Jensen RA",
            "Jing J",
            "Jukema JW",
            "Kajantie E",
            "Kamatani Y",
            "Kasbohm E",
            "Kaufman JM",
            "Kiemeney LA",
            "Kloppenburg M",
            "Kronenberg F",
            "Kubo M",
            "Lahti J",
            "Lapauw B",
            "Li S",
            "Liewald DCM",
            "Lim EM",
            "Linneberg A",
            "Marina M",
            "Mascalzoni D",
            "Matsuda K",
            "Medenwald D",
            "Meisinger C",
            "Meulenbelt I",
            "De Meyer T",
            "Meyer Zu Schwabedissen HE",
            "Mikolajczyk R",
            "Moed M",
            "Netea-Maier RT",
            "Nolte IM",
            "Okada Y",
            "Pala M",
            "Pattaro C",
            "Pedersen O",
            "Petersmann A",
            "Porcu E",
            "Postmus I",
            "Pramstaller PP",
            "Psaty BM",
            "Ramos YFM",
            "Rawal R",
            "Redmond P",
            "Richards JB",
            "Rietzschel ER",
            "Rivadeneira F",
            "Roef G",
            "Rotter JI",
            "Sala CF",
            "Schlessinger D",
            "Selvin E",
            "Slagboom PE",
            "Soranzo N",
            "S\u00f8rensen TIA",
            "Spector TD",
            "Starr JM",
            "Stott DJ",
            "Taes Y",
            "Taliun D",
            "Tanaka T",
            "Thuesen B",
            "Tiller D",
            "Toniolo D",
            "Uitterlinden AG",
            "Visser WE",
            "Walsh JP",
            "Wilson SG",
            "Wolffenbuttel BHR",
            "Yang Q",
            "Zheng HF",
            "Cappola A",
            "Peeters RP",
            "Naitza S",
            "V\u00f6lzke H",
            "Sanna S",
            "K\u00f6ttgen A",
            "Visser TJ",
            "Medici M"
        ],
        "doi": "10.1038/s41467-018-06356-1",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "141",
        "volume": "9",
        "issue": "1",
        "pages": "4455",
        "pre": false,
        "pdate": "2018-10-28"
    },
    "10.1186/s12967-015-0704-9": {
        "title": "The Cooperative Health Research in South Tyrol (CHRIS) study: rationale, objectives, and preliminary results.",
        "journal": "Journal of translational medicine",
        "year": "2015",
        "abstract": "The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment.",
        "authors": [
            "Pattaro C",
            "G\u00f6gele M",
            "Mascalzoni D",
            "Melotti R",
            "Schwienbacher C",
            "De Grandi A",
            "Foco L",
            "D'Elia Y",
            "Linder B",
            "Fuchsberger C",
            "Minelli C",
            "Egger C",
            "Kofink LS",
            "Zanigni S",
            "Sch\u00e4fer T",
            "Facheris MF",
            "Sm\u00e1rason SV",
            "Rossini A",
            "Hicks AA",
            "Weiss H",
            "Pramstaller PP"
        ],
        "doi": "10.1186/s12967-015-0704-9",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "135",
        "volume": "13",
        "issue": "",
        "pages": "348",
        "pre": false,
        "pdate": "2015-11-07"
    },
    "10.1038/s41598-019-48402-y": {
        "title": "Evaluation of the role of STAP1 in Familial Hypercholesterolemia.",
        "journal": "Scientific reports",
        "year": "2019",
        "abstract": "Familial hypercholesterolemia (FH) is characterised by elevated serum levels of low-density lipoprotein cholesterol (LDL-C) and a substantial risk for cardiovascular disease. The autosomal-dominant FH is mostly caused by mutations in *LDLR* (low density lipoprotein receptor), *APOB* (apolipoprotein B), and *PCSK9* (proprotein convertase subtilisin/kexin). Recently, *STAP1* has been suggested as a fourth causative gene. We analyzed *STAP1* in 75 hypercholesterolemic patients from Berlin, Germany, who are negative for mutations in canonical FH genes. In 10 patients with negative family history, we additionally screened for disease causing variants in *LDLRAP1* (low density lipoprotein receptor adaptor protein 1), associated with autosomal-recessive hypercholesterolemia. We identified one *STAP1* variant predicted to be disease causing. To evaluate association of serum lipid levels and *STAP1* carrier status, we analyzed 20 individuals from a population based cohort, the Cooperative Health Research in South Tyrol (CHRIS) study, carrying rare STAP1 variants. Out of the same cohort we randomly selected 100 non-carriers as control. In the Berlin FH cohort *STAP1* variants were rare. In the CHRIS cohort, we obtained no statistically significant differences between carriers and non-carriers of *STAP1* variants with respect to lipid traits. Until such an association has been verified in more individuals with genetic variants in *STAP1*, we cannot estimate whether *STAP1* generally is a causative gene for FH.",
        "authors": [
            "Danyel M",
            "Ott CE",
            "Grenkowitz T",
            "Salewsky B",
            "Hicks AA",
            "Fuchsberger C",
            "Steinhagen-Thiessen E",
            "Bobbert T",
            "Kassner U",
            "Demuth I"
        ],
        "doi": "10.1038/s41598-019-48402-y",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "130",
        "volume": "9",
        "issue": "1",
        "pages": "11995",
        "pre": false,
        "pdate": "2019-08-21"
    },
    "10.1038/s41467-019-12283-6": {
        "title": "Associations of autozygosity with a broad range of human phenotypes.",
        "journal": "Nature communications",
        "year": "2019",
        "abstract": "In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F<sub>ROH</sub>) for >1.4 million individuals, we show that F<sub>ROH</sub> is significantly associated (*p*\u2009<\u20090.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F<sub>ROH</sub> equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F<sub>ROH</sub> are confirmed within full-sibling pairs, where the variation in F<sub>ROH</sub> is independent of all environmental confounding.",
        "authors": [
            "Clark DW",
            "Okada Y",
            "Moore KHS",
            "Mason D",
            "Pirastu N",
            "Gandin I",
            "Mattsson H",
            "Barnes CLK",
            "Lin K",
            "Zhao JH",
            "Deelen P",
            "Rohde R",
            "Schurmann C",
            "Guo X",
            "Giulianini F",
            "Zhang W",
            "Medina-Gomez C",
            "Karlsson R",
            "Bao Y",
            "Bartz TM",
            "Baumbach C",
            "Biino G",
            "Bixley MJ",
            "Brumat M",
            "Chai JF",
            "Corre T",
            "Cousminer DL",
            "Dekker AM",
            "Eccles DA",
            "van Eijk KR",
            "Fuchsberger C",
            "Gao H",
            "Germain M",
            "Gordon SD",
            "de Haan HG",
            "Harris SE",
            "Hofer E",
            "Huerta-Chagoya A",
            "Igartua C",
            "Jansen IE",
            "Jia Y",
            "Kacprowski T",
            "Karlsson T",
            "Kleber ME",
            "Li SA",
            "Li-Gao R",
            "Mahajan A",
            "Matsuda K",
            "Meidtner K",
            "Meng W",
            "Montasser ME",
            "van der Most PJ",
            "Munz M",
            "Nutile T",
            "Palviainen T",
            "Prasad G",
            "Prasad RB",
            "Priyanka TDS",
            "Rizzi F",
            "Salvi E",
            "Sapkota BR",
            "Shriner D",
            "Skotte L",
            "Smart MC",
            "Smith AV",
            "van der Spek A",
            "Spracklen CN",
            "Strawbridge RJ",
            "Tajuddin SM",
            "Trompet S",
            "Turman C",
            "Verweij N",
            "Viberti C",
            "Wang L",
            "Warren HR",
            "Wootton RE",
            "Yanek LR",
            "Yao J",
            "Yousri NA",
            "Zhao W",
            "Adeyemo AA",
            "Afaq S",
            "Aguilar-Salinas CA",
            "Akiyama M",
            "Albert ML",
            "Allison MA",
            "Alver M",
            "Aung T",
            "Azizi F",
            "Bentley AR",
            "Boeing H",
            "Boerwinkle E",
            "Borja JB",
            "de Borst GJ",
            "Bottinger EP",
            "Broer L",
            "Campbell H",
            "Chanock S",
            "Chee ML",
            "Chen G",
            "Chen YI",
            "Chen Z",
            "Chiu YF",
            "Cocca M",
            "Collins FS",
            "Concas MP",
            "Corley J",
            "Cugliari G",
            "van Dam RM",
            "Damulina A",
            "Daneshpour MS",
            "Day FR",
            "Delgado GE",
            "Dhana K",
            "Doney ASF",
            "D\u00f6rr M",
            "Doumatey AP",
            "Dzimiri N",
            "Ebenesersd\u00f3ttir SS",
            "Elliott J",
            "Elliott P",
            "Ewert R",
            "Felix JF",
            "Fischer K",
            "Freedman BI",
            "Girotto G",
            "Goel A",
            "G\u00f6gele M",
            "Goodarzi MO",
            "Graff M",
            "Granot-Hershkovitz E",
            "Grodstein F",
            "Guarrera S",
            "Gudbjartsson DF",
            "Guity K",
            "Gunnarsson B",
            "Guo Y",
            "Hagenaars SP",
            "Haiman CA",
            "Halevy A",
            "Harris TB",
            "Hedayati M",
            "van Heel DA",
            "Hirata M",
            "H\u00f6fer I",
            "Hsiung CA",
            "Huang J",
            "Hung YJ",
            "Ikram MA",
            "Jagadeesan A",
            "Jousilahti P",
            "Kamatani Y",
            "Kanai M",
            "Kerrison ND",
            "Kessler T",
            "Khaw KT",
            "Khor CC",
            "de Kleijn DPV",
            "Koh WP",
            "Kolcic I",
            "Kraft P",
            "Kr\u00e4mer BK",
            "Kutalik Z",
            "Kuusisto J",
            "Langenberg C",
            "Launer LJ",
            "Lawlor DA",
            "Lee IT",
            "Lee WJ",
            "Lerch MM",
            "Li L",
            "Liu J",
            "Loh M",
            "London SJ",
            "Loomis S",
            "Lu Y",
            "Luan J",
            "M\u00e4gi R",
            "Manichaikul AW",
            "Manunta P",
            "M\u00e1sson G",
            "Matoba N",
            "Mei XW",
            "Meisinger C",
            "Meitinger T",
            "Mezzavilla M",
            "Milani L",
            "Millwood IY",
            "Momozawa Y",
            "Moore A",
            "Morange PE",
            "Moreno-Mac\u00edas H",
            "Mori TA",
            "Morrison AC",
            "Muka T",
            "Murakami Y",
            "Murray AD",
            "de Mutsert R",
            "Mychaleckyj JC",
            "Nalls MA",
            "Nauck M",
            "Neville MJ",
            "Nolte IM",
            "Ong KK",
            "Orozco L",
            "Padmanabhan S",
            "P\u00e1lsson G",
            "Pankow JS",
            "Pattaro C",
            "Pattie A",
            "Polasek O",
            "Poulter N",
            "Pramstaller PP",
            "Quintana-Murci L",
            "R\u00e4ikk\u00f6nen K",
            "Ralhan S",
            "Rao DC",
            "van Rheenen W",
            "Rich SS",
            "Ridker PM",
            "Rietveld CA",
            "Robino A",
            "van Rooij FJA",
            "Ruggiero D",
            "Saba Y",
            "Sabanayagam C",
            "Sabater-Lleal M",
            "Sala CF",
            "Salomaa V",
            "Sandow K",
            "Schmidt H",
            "Scott LJ",
            "Scott WR",
            "Sedaghati-Khayat B",
            "Sennblad B",
            "van Setten J",
            "Sever PJ",
            "Sheu WH",
            "Shi Y",
            "Shrestha S",
            "Shukla SR",
            "Sigurdsson JK",
            "Sikka TT",
            "Singh JR",
            "Smith BH",
            "Stan\u010d\u00e1kov\u00e1 A",
            "Stanton A",
            "Starr JM",
            "Stefansdottir L",
            "Straker L",
            "Sulem P",
            "Sveinbjornsson G",
            "Swertz MA",
            "Taylor AM",
            "Taylor KD",
            "Terzikhan N",
            "Tham YC",
            "Thorleifsson G",
            "Thorsteinsdottir U",
            "Tillander A",
            "Tracy RP",
            "Tusi\u00e9-Luna T",
            "Tzoulaki I",
            "Vaccargiu S",
            "Vangipurapu J",
            "Veldink JH",
            "Vitart V",
            "V\u00f6lker U",
            "Vuoksimaa E",
            "Wakil SM",
            "Waldenberger M",
            "Wander GS",
            "Wang YX",
            "Wareham NJ",
            "Wild S",
            "Yajnik CS",
            "Yuan JM",
            "Zeng L",
            "Zhang L",
            "Zhou J",
            "Amin N",
            "Asselbergs FW",
            "Bakker SJL",
            "Becker DM",
            "Lehne B",
            "Bennett DA",
            "van den Berg LH",
            "Berndt SI",
            "Bharadwaj D",
            "Bielak LF",
            "Bochud M",
            "Boehnke M",
            "Bouchard C",
            "Bradfield JP",
            "Brody JA",
            "Campbell A",
            "Carmi S",
            "Caulfield MJ",
            "Cesarini D",
            "Chambers JC",
            "Chandak GR",
            "Cheng CY",
            "Ciullo M",
            "Cornelis M",
            "Cusi D",
            "Smith GD",
            "Deary IJ",
            "Dorajoo R",
            "van Duijn CM",
            "Ellinghaus D",
            "Erdmann J",
            "Eriksson JG",
            "Evangelou E",
            "Evans MK",
            "Faul JD",
            "Feenstra B",
            "Feitosa M",
            "Foisy S",
            "Franke A",
            "Friedlander Y",
            "Gasparini P",
            "Gieger C",
            "Gonzalez C",
            "Goyette P",
            "Grant SFA",
            "Griffiths LR",
            "Groop L",
            "Gudnason V",
            "Gyllensten U",
            "Hakonarson H",
            "Hamsten A",
            "van der Harst P",
            "Heng CK",
            "Hicks AA",
            "Hochner H",
            "Huikuri H",
            "Hunt SC",
            "Jaddoe VWV",
            "De Jager PL",
            "Johannesson M",
            "Johansson \u00c5",
            "Jonas JB",
            "Jukema JW",
            "Junttila J",
            "Kaprio J",
            "Kardia SLR",
            "Karpe F",
            "Kumari M",
            "Laakso M",
            "van der Laan SW",
            "Lahti J",
            "Laudes M",
            "Lea RA",
            "Lieb W",
            "Lumley T",
            "Martin NG",
            "M\u00e4rz W",
            "Matullo G",
            "McCarthy MI",
            "Medland SE",
            "Merriman TR",
            "Metspalu A",
            "Meyer BF",
            "Mohlke KL",
            "Montgomery GW",
            "Mook-Kanamori D",
            "Munroe PB",
            "North KE",
            "Nyholt DR",
            "O'connell JR",
            "Ober C",
            "Oldehinkel AJ",
            "Palmas W",
            "Palmer C",
            "Pasterkamp GG",
            "Patin E",
            "Pennell CE",
            "Perusse L",
            "Peyser PA",
            "Pirastu M",
            "Polderman TJC",
            "Porteous DJ",
            "Posthuma D",
            "Psaty BM",
            "Rioux JD",
            "Rivadeneira F",
            "Rotimi C",
            "Rotter JI",
            "Rudan I",
            "Den Ruijter HM",
            "Sanghera DK",
            "Sattar N",
            "Schmidt R",
            "Schulze MB",
            "Schunkert H",
            "Scott RA",
            "Shuldiner AR",
            "Sim X",
            "Small N",
            "Smith JA",
            "Sotoodehnia N",
            "Tai ES",
            "Teumer A",
            "Timpson NJ",
            "Toniolo D",
            "Tregouet DA",
            "Tuomi T",
            "Vollenweider P",
            "Wang CA",
            "Weir DR",
            "Whitfield JB",
            "Wijmenga C",
            "Wong TY",
            "Wright J",
            "Yang J",
            "Yu L",
            "Zemel BS",
            "Zonderman AB",
            "Perola M",
            "Magnusson PKE",
            "Uitterlinden AG",
            "Kooner JS",
            "Chasman DI",
            "Loos RJF",
            "Franceschini N",
            "Franke L",
            "Haley CS",
            "Hayward C",
            "Walters RG",
            "Perry JRB",
            "Esko T",
            "Helgason A",
            "Stefansson K",
            "Joshi PK",
            "Kubo M",
            "Wilson JF"
        ],
        "doi": "10.1038/s41467-019-12283-6",
        "source_study": [
            "CHRIS baseline"
        ],
        "ar": "125",
        "volume": "10",
        "issue": "1",
        "pages": "4957",
        "pre": false,
        "pdate": "2019-11-02"
    }
}