Ancestry-specific high-risk gene variant profiling unmasks diabetes-associated genes.

ABSTRACT: How ancestry-associated genetic variance affects disparities in the risk of polygenic diseases and influences the identification of disease-associated genes warrants a deeper understanding. We hypothesized that the discovery of genes associated with polygenic diseases may be limited by the overreliance on single-nucleotide polymorphism (SNP)-based genomic investigation, as most significant variants identified in genome-wide SNP association studies map to introns and intergenic regions of the genome. To overcome such potential limitations, we developed a gene-constrained, function-based analytical method centered on high-risk variants (hrV) that encode frameshifts, stopgains or splice site disruption. We analyzed the total number of hrV per gene in populations of different ancestry, represe

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11000659 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature