Epistatic contributions to human traits via transcription factor mechanisms.

ABSTRACT: Epistasis causes an individual's genetic background to modulate a DNA variant's effect on trait [1-6]. Epistatic interactions among different loci in human complex traits are expected to be widespread but have not been found [7]. This could be due to small interaction effect sizes, the statistical complexity of estimating interactions that is higher than marginal variant effects, and a substantial multiple testing burden in a genome-wide scan [8-11]. Targeting interacting variants that contribute to the same biological pathway could lighten this burden. Here we combined Targeted Machine Learning [12, 13] with experimentally verified differential binding variants across 9 nuclear hormone receptors (NHR) to identify 535 two-point DNA variant-variant and 185 three-point variant-variant-sex NH

SUBMITTER: Roskams-Hieter B 

PROVIDER: S-EPMC12622120 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature