Estimation of Direct and Indirect Polygenic Effects and Gene-Environment Interactions using Polygenic Scores in Case-Parent Trio Studies.

ABSTRACT: Family-based studies provide a unique opportunity to characterize genetic risks of diseases in the presence of population structure, assortative mating, and indirect genetic effects. We propose a novel framework, PGS-TRI, for the analysis of polygenic scores (PGS) in case-parent trio studies to estimate the risk of an index condition associated with direct effects of inherited PGS, indirect effects of parental PGS, and gene-environment interactions. Extensive simulation studies demonstrate the robustness of PGS-TRI in the presence of complex population structure and assortative mating. We applied PGS-TRI to multi-ancestry trio studies of autism spectrum disorders (ASD) ( Ntrio=18,383 ), deriving transmission-based estimates of risk for the direct effects of established PGS for ASD and othe

SUBMITTER: Wang Z 

PROVIDER: S-EPMC11482979 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature