Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro.

ABSTRACT: Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity but has a high multiple testing burden in the context of genome-wide association studies (GWAS). We adapt a colocalization method, SharePro, to account for effect heterogeneity in fine-mapping and identify candidates for GxE analysis with reduced multiple testing burden. SharePro demonstrates improved power for both fine-mapping and GxE analysis compared to existing methods as well as well-controlled false type I error in simulations. Using smoking status stratified GWAS summary statistics, we identify genetic effects on lung function modulated by smoking status that are not identified by existing methods. Additionally, using sex stratified GWAS summary statistics, we character

SUBMITTER: Zhang W 

PROVIDER: S-EPMC11526169 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature