Global genetic differentiation of complex traits shaped by natural selection in humans

There are mean differences in complex traits among global human populations. We hypothesize that part of the phenotypic differentiation is due to natural selection. To address this hypothesis, we assess the differentiation in allele frequencies of trait-associated SNPs among African, Eastern Asian, and European populations for ten complex traits using data of large sample size (up to similar to 405,000). We show that SNPs associated with height (P = 2.46x 10(-5)), waist-to-hip ratio (P = 2.77x 10(-4)), and schizophrenia (P = 3.96x 10(-5)) are significantly more differentiated among populations than matched control SNPs, suggesting that these trait-associated SNPs have undergone natural selection. We further find that SNPs associated with height (P = 2.01x 10(-6)) and schizophrenia (P = 5.16x 10(-18)) show significantly higher variance in linkage disequilibrium (LD) scores across populations than control SNPs. Our results support the hypothesis that natural selection has shaped the genetic differentiation of complex traits, such as height and schizophrenia, among worldwide populations.