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

Yang, Jian, Bakshi, Andrew, Zhu, Zhihong, Hemani, Gibran, Vinkhuyzen, Anna A. E., Lee, Sang Hong, Robinson, Matthew R., Perry, John R. B., Nolte, Ilja M., van Vliet-Ostaptchouk, Jana V., Snieder, Harold, The LifeLines Cohort Study, Esko, Tonu, Milani, Lili, Maegi, Reedik, Metspalu, Andres, Hamsten, Anders, Magnusson, Patrik K. E., Pedersen, Nancy L., Ingelsson, Erik, Soranzo, Nicole, Keller, Matthew C., Wray, Naomi R., Goddard, Michael E. and Visscher, Peter M. (2015) Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nature Genetics, 47 10: 1114-1120. doi:10.1038/ng.3390


Author Yang, Jian
Bakshi, Andrew
Zhu, Zhihong
Hemani, Gibran
Vinkhuyzen, Anna A. E.
Lee, Sang Hong
Robinson, Matthew R.
Perry, John R. B.
Nolte, Ilja M.
van Vliet-Ostaptchouk, Jana V.
Snieder, Harold
The LifeLines Cohort Study
Esko, Tonu
Milani, Lili
Maegi, Reedik
Metspalu, Andres
Hamsten, Anders
Magnusson, Patrik K. E.
Pedersen, Nancy L.
Ingelsson, Erik
Soranzo, Nicole
Keller, Matthew C.
Wray, Naomi R.
Goddard, Michael E.
Visscher, Peter M.
Title Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2015-08-31
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ng.3390
Open Access Status Not Open Access
Volume 47
Issue 10
Start page 1114
End page 1120
Total pages 9
Place of publication New York, NY United States
Publisher Nature Publishing Group
Collection year 2016
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
UQ Diamantina Institute Publications
 
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