Phenome-wide association study in a Chinese population of 25,639 pregnant women Reveals loci associated with Maternal Comorbidities and Child Health
Phenome-wide association studies (PheWAS) have been less focused on maternal diseases and maternal-newborn comorbidities, especially in the Chinese population. To enhance our understanding of the genetic basis of these related diseases, we conducted a PheWAS on 25,639 pregnant women and 14,151 newborns in the Chinese Han population, using ultra-low-depth whole-genome sequence (ulcWGS). We identified 2,883 maternal trait-associated-SNPs associated with 26 phenotypes, among which 99.5% were near established GWAS loci. Further refinement delineated these SNPs to 442 unique trait-associated-loci (TAL) predicated on linkage-disequilibrium-R2>0.8, revealing that 75.6% demonstrated pleiotropy and 50.9% located in genes previously implicated in analogous phenotypes. Notably, we discovered 21 maternal SNPs associated with 35 neonatal phenotypes, including two SNPs associated with identical complications in both mothers and children. These findings underscore the importance of integrating ulcWGS data to enrich the discoveries derived from traditional PheWAS approaches.