Signatures of negative selection in the genetic architecture of human complex traits.
Zeng J., de Vlaming R., Wu Y., Robinson MR., Lloyd-Jones LR., Yengo L., Yap CX., Xue A., Sidorenko J., McRae AF., Powell JE., Montgomery GW., Metspalu A., Esko T., Gibson G., Wray NR., Visscher PM., Yang J.
We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (P