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Title: Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits
Contributor(s): Zhu, Zhihong (author); Bakshi, Andrew (author); Milani, Lili (author); Magi, Reedik (author); Metspalu, Andres (author); Hill, William G (author); Weir, Bruce S (author); Goddard, Michael E (author); Visscher, Peter M (author); Yang, Jian (author); Vinkhuyzen, Anna A E (author); Hemani, Gibran (author); Lee, Sang Hong  (author); Nolte, Ilja M (author); van Vliet-Ostaptchouk, Jana V (author); Snieder, Harold (author); The LifeLines Cohort Study, (author); Esko, Tonu (author)
Publication Date: 2015
Open Access: Yes
DOI: 10.1016/j.ajhg.2015.01.001Open Access Link
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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 (h2 SNP and δ2 SNP) in unrelated individuals based on an orthogonal model where the estimate of h2 SNP is independent of that of δ2 SNP.With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans. The estimate of δ2 SNP averaged across all the 79 quantitative traits was 0.03, approximately a fifth of that for additive variation (average h2 SNP = 0.15). There were a few traits that showed substantial estimates of δ2 SNP, 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.
Publication Type: Journal Article
Source of Publication: American Journal of Human Genetics, 96(3), p. 377-385
Publisher: Cell Press
Place of Publication: United States of America
ISSN: 1537-6605
Fields of Research (FoR) 2008: 070201 Animal Breeding
060408 Genomics
060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
Fields of Research (FoR) 2020: 300305 Animal reproduction and breeding
310509 Genomics
310506 Gene mapping
Socio-Economic Objective (SEO) 2008: 970106 Expanding Knowledge in the Biological Sciences
970107 Expanding Knowledge in the Agricultural and Veterinary Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
Socio-Economic Objective (SEO) 2020: 280102 Expanding knowledge in the biological sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

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