Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution.

ABSTRACT: Overall adiposity and body fat distribution are heritable traits associated with altered risk of cardiometabolic disease and mortality. Performing rare variant (minor allele frequency<1%) association testing using exome-sequencing data from 402,375 participants in the UK Biobank (UKB) for nine overall and tissue-specific fat distribution traits, we identified 19 genes where putatively damaging rare variation associated with at least one trait (Bonferroni-adjusted P<1.58×10^-7) and 52 additional genes at FDR≤1% (P≤4.37×10^-5). These 71 genes exhibited higher (P=3.58×10^-18) common variant prioritisation scores than genes not significantly enriched for rare putatively damaging variation, with evidence of monotonic allelic series (dose-respon

SUBMITTER: Baya NA 

PROVIDER: S-EPMC11451655 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature