A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects.

ABSTRACT: The contribution of genetic interactions (epistasis) to human complex trait variation remains poorly understood due, in part, to the statistical and computational challenges involved in testing for interaction effects. Here we introduce FAME (FAst Marginal Epistasis test), a method that can test for marginal epistasis of a single-nucleotide polymorphism (SNP) on a quantitative trait (whether the effect of an SNP on the trait is modulated by genetic background). FAME is computationally efficient, enabling tests of marginal epistasis on biobank-scale data. Applying FAME to genome-wide association study (GWAS)-significant trait-SNP associations across 53 quantitative traits and ≈300 000 unrelated White British individuals in the UK Biobank (UKBB), we identified 16 significant marginal epistas

SUBMITTER: Fu B 

PROVIDER: S-EPMC12695669 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature