Polygenic architecture of rare coding variation across 394,783 exomes.

ABSTRACT: Both common and rare genetic variants influence complex traits and common diseases. Genome-wide association studies have identified thousands of common-variant associations, and more recently, large-scale exome sequencing studies have identified rare-variant associations in hundreds of genes^1-3. However, rare-variant genetic architecture is not well characterized, and the relationship between common-variant and rare-variant architecture is unclear⁴. Here we quantify the heritability explained by the gene-wise burden of rare coding variants across 22 common traits and diseases in 394,783 UK Biobank exomes⁵. Rare coding variants (allele frequency < 1 × 10^-3) explain 1.3% (s.e. = 0.03%) of phenotypic variance on average-much less than common variant

SUBMITTER: Weiner DJ 

PROVIDER: S-EPMC10614218 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature