Signatures of negative selection in the genetic architecture of human complex traits.

Détails

ID Serval
serval:BIB_C471A4CF3F15
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Signatures of negative selection in the genetic architecture of human complex traits.
Périodique
Nature Genetics
Auteur(s)
Zeng J., de Vlaming R., Wu Y., Robinson M.R., Lloyd-Jones L.R., Yengo L., Yap C.X., Xue A., Sidorenko J., McRae A.F., Powell J.E., Montgomery G.W., Metspalu A., Esko T., Gibson G., Wray N.R., Visscher P.M., Yang J.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
50
Numéro
5
Pages
746-753
Langue
anglais
Résumé
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 < 0.05/28) signatures of natural selection in the genetic architecture of 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. The significant estimates of the relationship between effect size and minor allele frequency in complex traits are consistent with a model of negative (or purifying) selection, as confirmed by forward simulation. We conclude that negative selection acts pervasively on the genetic variants associated with human complex traits.
Pubmed
Web of science
Création de la notice
19/04/2018 18:22
Dernière modification de la notice
18/05/2018 6:26
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