Distinct explanations underlie gene-environment interactions in the UK Biobank.

ABSTRACT: The role of gene-environment (GxE) interaction in disease and complex trait architectures is widely hypothesized but currently unknown. Here, we apply three statistical approaches to quantify and distinguish three different types of GxE interaction for a given trait and environmental (E) variable. First, we detect locus-specific GxE interaction by testing for genetic correlation (r_g) < 1 across E bins. Second, we detect genome-wide effects of the E variable on genetic variance by leveraging polygenic risk scores (PRSs) to test for significant PRSxE in a regression of phenotypes on PRS, E, and PRSxE, together with differences in SNP heritability across E bins. Third, we detect genome-wide proportional amplification of genetic and environmental effects as a function of the E varia

SUBMITTER: Durvasula A 

PROVIDER: S-EPMC11947178 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature