Multivariate GWAS framework for family trios with parental phenotypes to control dynastic effects

Background

Effect size estimates in genome-wide association studies (GWAS) and Mendelian randomization (MR) based on unrelated individuals are often confounded by dynastic effects (DE). Existing family-trio-based methods can mitigate this bias, but they typically discard parental phenotypes and cannot jointly model multiple correlated traits. We propose FT-SEM, a multivariate GWAS framework that uses structural equation modeling for family trio data, with the aim of integrating genotypes and phenotypes from parents and offspring across multiple traits to estimate direct genetic effects on a shared latent factor.