Detecting Genotype-Population Interaction Effects by Ancestry Principal Components

Chenglong Yu, Guiyan Ni, Julius van der Werf, S. Hong Lee

Research output: Contribution to journalArticle

Abstract

Heterogeneity in the phenotypic mean and variance across populations is often observed for complex traits. One way to understand heterogeneous phenotypes lies in uncovering heterogeneity in genetic effects. Previous studies on genetic heterogeneity across populations were typically based on discrete groups in populations stratified by different countries or cohorts, which ignored the difference of population characteristics for the individuals within each group and resulted in loss of information. Here, we introduce a novel concept of genotype-by-population (G × P) interaction where population is defined by the first and second ancestry principal components (PCs), which are less likely to be confounded with country/cohort-specific factors. We applied a reaction norm model fitting each of 70 complex traits with significant SNP-heritability and the PCs as covariates to examine G × P interactions across diverse populations including white British and other white Europeans from the UK Biobank (N = 22,229). Our results demonstrated a significant population genetic heterogeneity for behavioral traits such as age at first sexual intercourse and academic qualification. Our approach may shed light on the latent genetic architecture of complex traits that underlies the modulation of genetic effects across different populations.

Original languageEnglish
Article number379
JournalFrontiers in Genetics
Volume11
DOIs
Publication statusPublished - 21 Apr 2020

Keywords

  • SNP-based heritability
  • UK Biobank
  • complex traits
  • genetic heterogeneity
  • genotype-phenotype relationship
  • selection bias

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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