Ancestry-specific regulatory and disease architectures are likely due to cell-type-specific gene-by-environment interactions.

ABSTRACT: Multi-ancestry genome-wide association studies (GWAS) have highlighted the existence of variants with ancestry-specific effect sizes. Understanding where and why these ancestry-specific effects occur is fundamental to understanding the genetic basis of human diseases and complex traits. Here, we characterized genes differentially expressed across ancestries (ancDE genes) at the cell-type level by leveraging single-cell RNA-seq data in peripheral blood mononuclear cells for 21 individuals with East Asian (EAS) ancestry and 23 individuals with European (EUR) ancestry (172K cells); then, we tested if variants surrounding those genes were enriched in disease variants with ancestry-specific effect sizes by leveraging ancestry-matched GWAS of 31 diseases and complex traits (average N = 90

SUBMITTER: Wang J 

PROVIDER: S-EPMC10615008 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature