Gene-environment dependencies lead to collider bias in models with polygenic scores.
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ABSTRACT: The application of polygenic scores has transformed our ability to investigate whether and how genetic and environmental factors jointly contribute to the variation of complex traits. Modelling the complex interplay between genes and environment, however, raises serious methodological challenges. Here we illustrate the largely unrecognised impact of gene-environment dependencies on the identification of the effects of genes and their variation across environments. We show that controlling for heritable covariates in regression models that include polygenic scores as independent variables introduces endogenous selection bias when one or more of these covariates depends on unmeasured factors that also affect the outcome. This results in the problem of conditioning on a collider, which in tur
SUBMITTER: Akimova ET
PROVIDER: S-EPMC8097011 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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