Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits

Zhu, Zhihong, Bakshi, Andrew, Vinkhuyzen, Anna A. E., Hemani, Gibran, Lee, Sang Hong, Nolte, Ilja M., vanVliet-Ostaptchouk, Jana V., Snieder, Harold, Esko, Tonu, Milani, Lili, Magi, Reedik, Metspalu, Andres, Hill, William G., Weir, Bruce S., Goddard, Michael E., Visscher, Peter M. and Yang, Jian (2015) Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits. American Journal of Human Genetics, 96 3: 377-385. doi:10.1016/j.ajhg.2015.01.001

Author Zhu, Zhihong
Bakshi, Andrew
Vinkhuyzen, Anna A. E.
Hemani, Gibran
Lee, Sang Hong
Nolte, Ilja M.
vanVliet-Ostaptchouk, Jana V.
Snieder, Harold
Esko, Tonu
Milani, Lili
Magi, Reedik
Metspalu, Andres
Hill, William G.
Weir, Bruce S.
Goddard, Michael E.
Visscher, Peter M.
Yang, Jian
Title Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2015-02-12
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2015.01.001
Open Access Status
Volume 96
Issue 3
Start page 377
End page 385
Total pages 9
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2016
Language eng
Formatted abstract
For human complex traits, non-additive genetic variation has been invoked to explain “missing heritability,” but its discovery is often neglected in genome-wide association studies. Here we propose a method of using SNP data to partition and estimate the proportion of phenotypic variance attributed to additive and dominance genetic variation at all SNPs (View the MathML source and View the MathML source) in unrelated individuals based on an orthogonal model where the estimate of View the MathML source is independent of that of View the MathML source. With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans. The estimate of View the MathML source averaged across all the 79 quantitative traits was 0.03, approximately a fifth of that for additive variation (average View the MathML source = 0.15). There were a few traits that showed substantial estimates of View the MathML source, none of which were replicated in a larger sample of 11,965 individuals. We further performed genome-wide association analyses of the 79 quantitative traits and detected SNPs with genome-wide significant dominance effects only at the ABO locus for factor VIII and von Willebrand factor. All these results suggest that dominance variation at common SNPs explains only a small fraction of phenotypic variation for human complex traits and contributes little to the missing narrow-sense heritability problem.
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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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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