Evaluating significance of European-associated index SNPs in the East Asian population for 31 complex phenotypes

Abstract

Abstract Background Genome-wide association studies (GWASs) have identified many single-nucleotide polymorphisms (SNPs) associated with complex phenotypes in the European (EUR) population; however, the extent to which EUR-associated SNPs can be generalized to other populations such as East Asian (EAS) is not clear. Results By leveraging summary statistics of 31 phenotypes in the EUR and EAS populations, we first evaluated the difference in heritability between the two populations and calculated the trans-ethnic genetic correlation. We observed the heritability estimates of some phenotypes varied substantially across populations and 53.3% of trans-ethnic genetic correlations were significantly smaller than one. Next, we examined whether EUR-associated SNPs of these phenotypes could be identified in EAS using the trans-ethnic false discovery rate method while accounting for winner's curse for SNP effect in EUR and difference of sample sizes in EAS. We found on average 54.5% of EUR-associated SNPs were also significant in EAS. Furthermore, we discovered non-significant SNPs had higher effect heterogeneity, and significant SNPs showed more consistent linkage disequilibrium and allele frequency patterns between the two populations. We also demonstrated non-significant SNPs were more likely to undergo natural selection. Conclusions Our study revealed the extent to which EUR-associated SNPs could be significant in the EAS population and offered deep insights into the similarity and diversity of genetic architectures underlying phenotypes in distinct ancestral groups.