Polygenic risk scores: pleiotropy and the effect of environment.

ABSTRACT: Polygenic risk scores (PRSs) discriminate trait risks better than single genetic markers because they aggregate the effects of risk alleles from multiple genetic loci. Constructing pleiotropic PRSs and understanding heterogeneity, and the replication of PRS-trait associations can strengthen its applications. By using variational Bayesian multivariate high-dimensional regression, we constructed pleiotropic PRSs jointly associated with body mass index, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol in a sample of 18,108 Caucasians from three independent cohorts. We found that dissecting heterogeneity associated with birth year, which is a proxy of exogenous exposures, improved the replication of significant PRS-trait associations from 37.5% (6 of 16) in

SUBMITTER: Loika Y 

PROVIDER: S-EPMC7732954 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature