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Detecting genotype-population interaction effects by ancestry principal components

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dc.contributor.authorYu, C.
dc.contributor.authorNi, G.
dc.contributor.authorvan der Werf, J.
dc.contributor.authorLee, S.H.
dc.date.issued2020
dc.descriptionData source: Supplementary material, https://doi.org/10.3389/fgene.2020.00379
dc.description.abstractHeterogeneity 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.
dc.identifier.citationFrontiers in Genetics, 2020; 11(379):1-12
dc.identifier.doi10.3389/fgene.2020.00379
dc.identifier.issn1664-8021
dc.identifier.issn1664-8021
dc.identifier.urihttps://hdl.handle.net/11541.2/142397
dc.language.isoen
dc.publisherFrontiers Research Foundation
dc.relation.fundingARC DP190100766
dc.relation.fundingARC FT160100229
dc.relation.fundingNHMRC 1087889
dc.rightsCopyright 2020 Yu, Ni, van der Werf and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. (https://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.3389/fgene.2020.00379
dc.subjectgenotype-phenotype relationship
dc.subjectcomplex traits
dc.subjectSNP-based heritability
dc.subjectgenetic heterogeneity
dc.subjectUK Biobank
dc.subjectselection bias
dc.titleDetecting genotype-population interaction effects by ancestry principal components
dc.typeJournal article
pubs.publication-statusPublished
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