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<h1 class="title toc-ignore">Preparing UKBB reference files for genotype-based scoring</h1>
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<p>Reference files for genotype-based scoring having already been prepared based on the 1000 Genomes Phase 3 data. However, the sample size is relatively small which can reduce the accuracy of LD and MAF estimates, and has reduced genetic diversity. Here we will prepare reference files based on UK Biobank sample.</p>
<p>The imputed UK Biobank data has already been harmonised with 1KG Phase 3 reference. First we need to create a subset (N=10,000) of European indidivuals. Then create reference files based on these individuals.</p>
<p><br/></p>
<hr />
<div id="genotypic-data" class="section level1">
<h1><span class="header-section-number">1</span> Genotypic data</h1>
<p>In this section we will download the required reference genotype data, and format it for use.</p>
<details>
<p><summary>Set required variables for command line</summary></p>
<pre class="bash"><code># Set variables
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config</code></pre>
</details>
<p><br/></p>
<hr />
<div id="create-keep-file-for-10k-european-individuals" class="section level2">
<h2><span class="header-section-number">1.1</span> Create keep file for 10K European individuals</h2>
<p>We have already calculated ancestry PCs for UK biobank and identified European ancestry based on 1KG Phase participants. Now create a random subset of 10K European individuals, which aren’t in the phenotype files used for prediction modelling.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
mkdir -p ${UKBB_output}/UKBB_ref/keep_files
module add general/R/3.5.0
R
library(data.table)
# Read in environmental variables
source('/users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config')
# Read in list of EUR UKBB individuals
EUR_UKBB<-fread(paste0(UKBB_output, '/Projected_PCs/Ancestry_idenitfier/UKBB.w_hm3.AllAncestry.EUR.keep'))
names(EUR_UKBB)<-c('FID','IID')
# Read in list of individuals used for one of the phenotypes
pheno<-c('Depression','Intelligence','BMI','Height','T2D','CAD','IBD','MultiScler','RheuArth','Breast_Cancer','Prostate_Cancer')
pheno_all<-NULL
for(i in pheno){
pheno_tmp<-fread(paste0(UKBB_output, '/Phenotype/PRS_comp_subset/UKBB.',i,'.txt'))
pheno_all<-rbind(pheno_all,pheno_tmp[,1:2,with=F])
}
pheno_all<-pheno_all[!duplicated(paste(pheno_all$FID, pheno_all$IID, sep='-')),]
# List Eureopean individuals that are not in the phenotype files
pheno_all$UID<-paste(pheno_all$FID, pheno_all$IID, sep='-')
EUR_UKBB$UID<-paste(EUR_UKBB$FID, EUR_UKBB$IID, sep='-')
EUR_UKBB_nopheno<-EUR_UKBB[!(EUR_UKBB$UID %in% pheno_all$UID),]
# Extract a random 10K individual
set.seed(1)
EUR_UKBB_nopheno_10K<-EUR_UKBB_nopheno[sample(dim(EUR_UKBB_nopheno)[1],10000),]
EUR_UKBB_nopheno_10K$UID<-NULL
write.table(EUR_UKBB_nopheno_10K, paste0(UKBB_output, '/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep'), col.names=F, row.names=F, quote=F)
q()
n
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
</div>
<div id="make-plink-file-containing-10k-eur-subset" class="section level1">
<h1><span class="header-section-number">2</span> Make plink file containing 10K EUR subset</h1>
<p>To speed up subsequent analyses, we will create plink files for the 10K EUR subset of UKBB. We will also apply a SNP missingness threshold of 0.02 to retain SNPs that are available in nearly all indiviuals. We will also output .freq files</p>
<details>
<p><summary>Create plink dataset</summary></p>
<pre class="bash"><code># Set variables
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
mkdir ${UKBB_output}/UKBB_ref/genotype
# Create plink dataset
for chr in $(seq 1 22);do
qsub ${plink1_9} \
--bfile ${UKBB_output}/Genotype/Harmonised/UKBB.w_hm3.QCd.AllSNP.chr${chr} \
--make-bed \
--geno 0.02 \
--keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--out ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr${chr}
done
# Create frq files for the plink dataset
for chr in $(seq 1 22);do
qsub ${plink1_9} \
--bfile ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr${chr} \
--freq \
--out ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr${chr}
done
# Create genome-wide version of dataset for lassosum
ls ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr*.bed | sed -e 's/\.bed//g' > ${UKBB_output}/UKBB_ref/genotype/merge_list.txt
qsub ${plink1_9} \
--merge-list ${UKBB_output}/UKBB_ref/genotype/merge_list.txt \
--make-bed \
--out ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW
rm ${UKBB_output}/UKBB_ref/genotype/merge_list.txt
# Create a file listing the keep file
echo EUR ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep > ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
<div id="polygenic-scoring" class="section level1">
<h1><span class="header-section-number">3</span> Polygenic scoring</h1>
<p>In this section we will create files that can be used for polygenic scoring (score files), estimate the mean and SD of polygenic scores within different ancestries for scaling target samples. This will be performed using MAF and LD in the UKBB 10K European subset.</p>
<p>Polygenic scores are derived using multiple methods to allow comparison. After the best method has been idenitified, it will ony be necessary to calculate scores using the one method.</p>
<details>
<p><summary>Set required variables</summary></p>
<pre class="bash"><code># Set variables
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config</code></pre>
</details>
<p><br/></p>
<hr />
<div id="prepare-score-files-and-scaling-files-for-polygenic-scoring-pt-clump" class="section level2">
<h2><span class="header-section-number">3.1</span> Prepare score files and scaling files for polygenic scoring (pT + clump)</h2>
<p>Here I prepare reference files for typical polygenic scores derived using the p-value thresholding and LD-based clumping procedure.</p>
<div id="sparse-thresholding-nested" class="section level3">
<h3><span class="header-section-number">3.1.1</span> Sparse thresholding (nested)</h3>
<p>Here we will only use 8 p-value thresholds.</p>
<p>This section uses an R script called ‘polygenic_score_file_creator.R’. Further information the usage of this script can be found <a href="https://github.com/opain/GenoPred/tree/master/Scripts/polygenic_score_file_creator">here</a>.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir -p ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/todo.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/todo.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/sbatch.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 5G
#SBATCH -J pt_clump
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/todo.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator/polygenic_score_file_creator.R \
--ref_plink_chr ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--memory 3000 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/todo.txt | cut -d' ' -f1)%5 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/pt_clump/sbatch.sh
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
</div>
<div id="prepare-score-and-scale-files-for-polygenic-scoring-using-lassosum" class="section level2">
<h2><span class="header-section-number">3.2</span> Prepare score and scale files for polygenic scoring using lassosum</h2>
<p>Here we create reference files for polygenic scores calculated by lassosum, a method for performing lasso-based shrinkage to GWAS sumstats to account for LD and winners curse. More information on lassosum can be found <a href="https://github.com/tshmak/lassosum">here</a>. You will need to install the lassosum R package in advance.</p>
<p>This section uses an R script called ‘polygenic_score_file_creator_lassosum.R’. Further information the usage of this script can be found <a href="https://github.com/opain/GenoPred/tree/master/Scripts/polygenic_score_file_creator_lassosum">here</a>.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/todo.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/todo.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/sbatch.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 10G
#SBATCH -J lassosum
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/todo.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_lassosum/polygenic_score_file_creator_lassosum.R \
--ref_plink_gw ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--plink ${plink1_9} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/todo.txt | cut -d' ' -f1)%5 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/lassosum/sbatch.sh
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
<div id="prepare-score-and-scale-files-for-polygenic-scoring-using-s-blup" class="section level2">
<h2><span class="header-section-number">3.3</span> Prepare score and scale files for polygenic scoring using S-BLUP</h2>
<p>Here we create reference files for polygenic scores calculated by SBLUP, a method for performing genomic BLUP analysis with summary data and an LD-reference. More information on SBLUP can be found <a href="https://cnsgenomics.com/software/gcta/#Genomicriskprediction">here</a>. You will need to download the GCTA software in advance.</p>
<p>This section uses an R script called ‘polygenic_score_file_creator_SBLUP.R’. Further information the usage of this script can be found <a href="https://github.com/opain/GenoPred/tree/master/Scripts/polygenic_score_file_creator_SBLUP">here</a>.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/todo.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/todo.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/sbatch.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 80G
#SBATCH -n 6
#SBATCH -J SBLUP
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/todo.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_SBLUP/polygenic_score_file_creator_SBLUP.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--gcta ${gcta} \
--munge_sumstats ${munge_sumstats} \
--ldsc ${ldsc} \
--ldsc_ref ${ldsc_ref} \
--hm3_snplist ${HapMap3_snplist_dir}/w_hm3.snplist \
--memory 50000 \
--n_cores 6 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/todo.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBLUP/sbatch.sh
# Note. UKB reference has not been filtered for MAF > 0.01. And GWAS sumstats have only undergone QC with comparison to the 1KG Phase 3 reference. MAF discrepencies may exist unless the methods checks for this.
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
<div id="prepare-score-and-scale-files-for-polygenic-scoring-using-sbayesr" class="section level2">
<h2><span class="header-section-number">3.4</span> Prepare score and scale files for polygenic scoring using SBayesR</h2>
<p>Here we create reference files for polygenic scores calculated by SBayesR, a bayesian shrinkage method for GWAS summary data and an LD-reference. More information on SBayesR can be found <a href="http://cnsgenomics.com/software/gctb/#SummaryBayesianAlphabet">here</a>. You will need to download the GCTB software in advance.</p>
<p>First we need to create a specially formatted LD matrix for SBayesR. The GCTB authors compare the performance of SBayesR when using different datasets for LD matrix estimation. They show that using EUR 1KG data (N=378) leads to poorer prediction accuracy from S-BayesR. They then use LD matrices based on 50,000 random European individuals from UK Biobank to provide optimal prediction, however using 5000 indivduals gave similar results. I think we should be comparing PRS methods based on the same reference data, so we should estimate LD matrices based on the EUR 1KG reference. A subsequent study (by me) can test these PRS methods based on LD estimates from 5000 individuals.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# When retaining only EUR, I am getting an error saying fixed SNP. Create list of variants with MAF > 0.001.
# Download the required genetic maps
cd ${genetic_map}/CEU
for chr in $(seq 1 22); do
wget https://github.com/joepickrell/1000-genomes-genetic-maps/raw/master/interpolated_OMNI/chr${chr}.OMNI.interpolated_genetic_map.gz
done
gunzip *.gz
mkdir -p ${UKBB_output}/UKBB_ref/LD_matrix/EUR
module add apps/R/3.6.0
R
# Read in environmental variables
source('/users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config')
source('/users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config')
# Create list of SNPs that have MAF above 0.001 in the EUR 1KG sample
for(i in 1:22){
frq<-read.table(paste0(UKBB_output, '/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr',i,'.frq'), header=T)
frq<-frq[frq$MAF > 0.001,]
write.table(frq$SNP,paste0(UKBB_output, '/UKBB_ref/LD_matrix/EUR/SNP_maf0.001_EUR_chr',i,'.txt'), col.names=F, row.names=F, quote=F)
}
# Stop scientific notation
options(scipen=999)
# Create shrunk LD matrix in 5000 SNP pieces
for(i in 1:22){
nsnp<-system(paste0('wc -l ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/SNP_maf0.001_EUR_chr',i,'.txt'), intern=T)
nsnp<-as.numeric(unlist(strsplit(nsnp, ' '))[1])
nsnp_chunk<-ceiling(nsnp/5000)
for(j in 1:nsnp_chunk){
start<-(5000*(j-1))+1
end<-5000*j
print(start)
print(end)
system(paste0('sbatch -p brc,shared --mem 5G ',gctb,' --bfile ',UKBB_output,'/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.chr',i,' --make-shrunk-ldm --extract ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/SNP_maf0.001_EUR_chr',i,'.txt --gen-map ',genetic_map,'/CEU/chr',i,'.OMNI.interpolated_genetic_map --snp ',start,'-',end,' --out ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr',i))
}
}
# Merge the chunks into per chromosome LD matrices
for(i in 1:22){
nsnp<-system(paste0('wc -l ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/SNP_maf0.001_EUR_chr',i,'.txt'), intern=T)
nsnp<-as.numeric(unlist(strsplit(nsnp, ' '))[1])
nsnp_chunk<-ceiling(nsnp/5000)
files<-list.files(path=paste0(UKBB_output,'/UKBB_ref/LD_matrix/EUR/'), pattern=paste0('UKBB.noPheno.EUR.10K.chr',i,'.snp'))
files<-files[grepl('.bin',files)]
files<-paste0(UKBB_output,'/UKBB_ref/LD_matrix/EUR/',files)
if(length(files) == nsnp_chunk){
files<-gsub('.bin', '', files)
file_num<-gsub('.*.snp', '', files)
file_num<-as.numeric(gsub('-.*', '', file_num))
files<-files[order(file_num)]
# Sort files in order of genomic location otherwise SBayeR does not converge!
write.table(files,paste0(UKBB_output,'/UKBB_ref/LD_matrix/EUR/shrunk_ld_chr',i,'merge_list'), col.names=F, row.names=F, quote=F)
system(paste0('sbatch -p brc,shared --mem ',round(2.5*nsnp_chunk),'G ',gctb,' --mldm ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/shrunk_ld_chr',i,'merge_list --make-shrunk-ldm --out ',UKBB_output,'/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr',i))
} else {
print('Not all chunks finished')
print(files)
}
}
q()
n
# Delete temporary files
for chr in $(seq 1 22);do
rm ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr${chr}.snp*
rm ${UKBB_output}/UKBB_ref/LD_matrix/EUR/SNP_maf0.001_EUR_chr${chr}.txt
rm ${UKBB_output}/UKBB_ref/LD_matrix/EUR/shrunk_ld_chr${chr}merge_list
done
# Make the LD matrices sparse
for chr in $(seq 1 22);do
sbatch -p brc,shared --mem 50G ${gctb} --ldm ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr${chr}.ldm.shrunk --chisq 0 --make-sparse-ldm --out ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr${chr}
done
# Delete temporary files
for chr in $(seq 1 22);do
rm ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr${chr}.ldm.shrunk.*
done
# Make a list of shrunk sparse matrices
ls ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr*.ldm.sparse.bin | sed "s/.bin//" > ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.sparse.ldm.list</code></pre>
</details>
<p><br/></p>
<p>Now the LD reference is ready, we can calculate SBayesR shrunk GWAS summary statistics. This section uses an R script called ‘polygenic_score_file_creator_SBayes.R’. Further information the usage of this script can be found <a href="https://github.com/opain/GenoPred/tree/master/Scripts/polygenic_score_file_creator_SBayesR">here</a>.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>################
# Using UKBB reference
################
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 50G
#SBATCH -n 6
#SBATCH -J SBayesR
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_SBayesR/polygenic_score_file_creator_SBayesR.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--gctb ${gctb} \
--ld_matrix_chr ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr \
--memory 50000 \
--n_cores 6 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch.sh
#########
# Note.
# GCTB performance is highly variable. This is thought to be due to the quality of the GWAS summary statistics. This is in some cases due to poor convergence. The authors suggest restricting the analysis to SNPs with a p-value < 0.4
########
################
# Using UKBB reference (P<0.4)
################
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_P4.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_P4/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_P4.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_P4.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 50G
#SBATCH -n 6
#SBATCH -J SBayesR
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_P4.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_SBayesR/polygenic_score_file_creator_SBayesR.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--gctb ${gctb} \
--ld_matrix_chr ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr \
--memory 50000 \
--n_cores 6 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_P4/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list \
--P_max 0.4
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_P4.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_P4.sh
################
# Using UKBB reference using GCTB v2.03
################
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_GCTB_203/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_GCTB_203.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 50G
#SBATCH -n 6
#SBATCH -J SBayesR
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_SBayesR/polygenic_score_file_creator_SBayesR.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--gctb ${gctb_203} \
--ld_matrix_chr ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr \
--memory 50000 \
--n_cores 6 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_GCTB_203/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_GCTB_203.sh
################
# Using UKBB reference using GCTB v2.03 with forced robust parameterisation
################
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203_robust.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_GCTB_203_robust/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203_robust.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_GCTB_203_robust.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 50G
#SBATCH -n 6
#SBATCH -J SBayesR
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203_robust.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_SBayesR/polygenic_score_file_creator_SBayesR.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--gctb ${gctb_203} \
--ld_matrix_chr ${UKBB_output}/UKBB_ref/LD_matrix/EUR/UKBB.noPheno.EUR.10K.chr \
--memory 50000 \
--robust T \
--n_cores 6 \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/${gwas}_GCTB_203_robust/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/todo_GCTB_203_robust.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/SBayesR/sbatch_GCTB_203_robust.sh
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
<div id="prepare-score-and-scale-files-for-polygenic-scoring-using-ldpred" class="section level2">
<h2><span class="header-section-number">3.5</span> Prepare score and scale files for polygenic scoring using LDPred</h2>
<p>Here we create reference files for polygenic scores calculated by LDPred, a method for performing bayesian shrinkage analysis with summary data and an LD-reference. More information on LDPred can be found <a href="https://github.com/bvilhjal/ldpred">here</a>.</p>
<p>This section uses an R script called ‘polygenic_score_file_creator_LDPred.R’. Further information the usage of this script can be found <a href="https://github.com/opain/GenoPred/tree/master/Scripts/polygenic_score_file_creator_LDPred">here</a>.</p>
<details>
<p><summary>Show code</summary></p>
<pre class="bash"><code>. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
# Create directory
mkdir ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred
# Create file listing GWAS that haven't been processed.
> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/todo.txt
for gwas in $(echo DEPR06 COLL01 HEIG03 BODY04 DIAB05 COAD01 CROH01 SCLE03 RHEU02 EDUC03 ADHD04 BODY11 PRCA01 BRCA01);do
if [ ! -f ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas}.EUR.scale ]; then
echo $gwas >> ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/todo.txt
fi
done
# Create shell script to run using sbatch
cat > ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/sbatch.sh << 'EOF'
#!/bin/sh
#SBATCH -p shared,brc
#SBATCH --mem 50G
#SBATCH -n 1
#SBATCH -J LDPred
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Target_scoring.config
. /users/k1806347/brc_scratch/Software/MyGit/GenoPred/config_used/Pipeline_prep.config
gwas=$(sed "${SLURM_ARRAY_TASK_ID}q;d" ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/todo.txt)
echo ${gwas}
/users/k1806347/brc_scratch/Software/Rscript.sh /users/k1806347/brc_scratch/Software/MyGit/GenoPred/Scripts/polygenic_score_file_creator_LDPred/polygenic_score_file_creator_LDPred.R \
--ref_plink ${UKBB_output}/UKBB_ref/genotype/UKBB.noPheno.EUR.10K.GW \
--ref_keep ${UKBB_output}/UKBB_ref/keep_files/UKBB_noPheno_EUR_10K.keep \
--sumstats ${gwas_rep_qcd}/${gwas}.cleaned.gz \
--plink ${plink1_9} \
--memory 20000 \
--n_cores 1 \
--ldpred ${ldpred} \
--output ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/${gwas}/UKBB.noPheno.EUR.10K.w_hm3.${gwas} \
--ref_pop_scale ${UKBB_output}/UKBB_ref/keep_files/keep_file.list
EOF
sbatch --array 1-$(wc -l ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/todo.txt | cut -d' ' -f1)%3 ${UKBB_output}/UKBB_ref/Score_files_for_polygenic/LDPred/sbatch.sh
</code></pre>
</details>
<p><br/></p>
<hr />
</div>
<div id="prepare-score-and-scale-files-for-polygenic-scoring-using-ldpred2" class="section level2">