Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.

Details

Serval ID
serval:BIB_808E5C6B49E0
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.
Journal
Nature Genetics
Author(s)
Yang J., Bakshi A., Zhu Z., Hemani G., Vinkhuyzen A.A., Lee S.H., Robinson M.R., Perry J.R., Nolte I.M., van Vliet-Ostaptchouk J.V., Snieder H., Esko T., Milani L., Mägi R., Metspalu A., Hamsten A., Magnusson P.K., Pedersen N.L., Ingelsson E., Soranzo N., Keller M.C., Wray N.R., Goddard M.E., Visscher P.M.
Working group(s)
LifeLines Cohort Study
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
47
Number
10
Pages
1114-1120
Language
english
Abstract
We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that ∼97% and ∼68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all ∼17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices.

Keywords
Body Height/genetics, Body Mass Index, Genetic Variation, Genome, Human, Humans
Pubmed
Web of science
Create date
06/12/2017 13:42
Last modification date
20/08/2019 15:41
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