TY - JOUR
T1 - Detecting Genotype-Population Interaction Effects by Ancestry Principal Components
AU - Yu, Chenglong
AU - Ni, Guiyan
AU - van der Werf, Julius
AU - Lee, S. Hong
PY - 2020/4/21
Y1 - 2020/4/21
N2 - 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.
AB - 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.
KW - complex traits
KW - genetic heterogeneity
KW - genotype-phenotype relationship
KW - selection bias
KW - SNP-based heritability
KW - UK Biobank
UR - http://www.scopus.com/inward/record.url?scp=85084265119&partnerID=8YFLogxK
U2 - 10.3389/fgene.2020.00379
DO - 10.3389/fgene.2020.00379
M3 - Article
AN - SCOPUS:85084265119
SN - 1664-8021
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 379
ER -