Journal article
Dominance genetic variation contributes little to the missing heritability for human complex traits
Z Zhu, A Bakshi, AAE Vinkhuyzen, G Hemani, SH Lee, IM Nolte, JV Van Vliet-Ostaptchouk, H Snieder, T Esko, L Milani, R Mägi, A Metspalu, WG Hill, BS Weir, ME Goddard, PM Visscher, J Yang
American Journal of Human Genetics | Published : 2015
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 (hSNP2 and δSNP2) in unrelated individuals based on an orthogonal model where the estimate of hSNP2 is independent of that of δSNP2. With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans. The estimate of δSNP2 averaged across all the 79 quantitative traits was 0.03, approximately a fifth of that for additi..
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Awarded by Sylvia and Charles Viertel Charitable Foundation
Funding Acknowledgements
This research was supported by the Australian Research Council (130102666), the Australian National Health and Medical Research Council (1052684, 613601, 1048853), the USA NIH (GM057091, GM099568, MH100141), the Sylvia & Charles Viertel Charitable Foundation, and the UQ Foundation. This study makes use of data from the database of Genotypes and Phenotypes (dbGaP) under accession phs000090, the Lifelines study, and the EGCUT study (see the Supplemental Acknowledgments for the full set of acknowledgments for these data).