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

Jing Guo, Yang Wu, Zhihong Zhu, Zhili Zheng, Maciej Trzaskowski, Jian Zeng, Matthew R. Robinson, Peter M. Visscher and Jian Yang ()
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Jing Guo: The University of Queensland
Yang Wu: The University of Queensland
Zhihong Zhu: The University of Queensland
Zhili Zheng: The University of Queensland
Maciej Trzaskowski: The University of Queensland
Jian Zeng: The University of Queensland
Matthew R. Robinson: The University of Queensland
Peter M. Visscher: The University of Queensland
Jian Yang: The University of Queensland

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract 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 ~405,000). We show that SNPs associated with height ( $$P = 2.46 \times 10^{ - 5}$$ P = 2.46 × 1 0 - 5 ), waist-to-hip ratio ( $$P = 2.77 \times 10^{ - 4}$$ P = 2.77 × 1 0 - 4 ), and schizophrenia ( $$P = 3.96 \times 10^{ - 5}$$ P = 3.96 × 1 0 - 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 ( $$P = 2.01 \times 10^{ - 6}$$ P = 2.01 × 1 0 - 6 ) and schizophrenia ( $$P = 5.16 \times 10^{ - 18}$$ P = 5.16 × 1 0 - 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.

Date: 2018
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DOI: 10.1038/s41467-018-04191-y

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