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

Details

Serval ID
serval:BIB_C471A4CF3F15
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Signatures of negative selection in the genetic architecture of human complex traits.
Journal
Nature genetics
Author(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
Publication state
Published
Issued date
05/2018
Peer-reviewed
Oui
Volume
50
Number
5
Pages
746-753
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Bayes Theorem, Gene Frequency/genetics, Genome-Wide Association Study/methods, Genotype, Humans, Linear Models, Models, Genetic, Multifactorial Inheritance/genetics, Phenotype, Polymorphism, Single Nucleotide/genetics, Quantitative Trait, Heritable, Selection, Genetic/genetics
Pubmed
Web of science
Create date
19/04/2018 18:22
Last modification date
20/08/2019 16:39
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