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Common SNPs explain a large proportion of the heritability for human height

Nature Genetics volume 42, pages 565–569 (2010)Cite this article

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Abstract

SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.

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Figure 1: Prediction error of genetic relationship.
Figure 2: Estimates of variance explained by genome-wide SNPs from adjusted estimates of genetic relationships are unbiased.
Figure 3: All pairwise comparisons contribute to the estimate of genetic variance.

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Change history

  • 24 September 2010

    In the version of this supplementary file originally posted online, Supplementary Fig. 2a and 2b were incorrect. The legend stated that in Supplementary Fig. 2a, PC1 versus PC2 was plotted when in fact PC2 versus PC3 was shown. Similarly, in Supplementary Fig. 2b, PC4 versus PC5 was plotted rather than PC3 versus PC4 as stated. This error is purely graphical and does not in any way affect the results or conclusions presented in the article. We thank Andrew Stewart for kindly pointing out this error to us. The authors regret not detecting this error earlier. The error has been corrected in this file as of 24 September 2010.

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Acknowledgements

We are grateful to the twins and their families for their generous participation in these studies. We would like to thank staff at the Queensland Institute of Medical Research: D. Statham, A. Eldridge and M. Grace for sample collection, M. Campbell, L. Bowdler, S. Crooks and staff of the Molecular Epidemiology Laboratory for sample processing and preparation, B. Cornes for height data preparation, D. Smyth and H. Beeby for IT support and A. McRae and H. Lee for discussions. We thank N. Wray for helpful comments on the manuscript. We acknowledge funding from the Australian National Health and Medical Research Council (grants 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688 and 552485), the US National Institutes of Health (grants AA07535, AA10248, AA014041, AA13320, AA13321, AA13326 and DA12854) and the Australian Research Council (grant DP0770096).

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Authors and Affiliations

  1. Queensland Institute of Medical Research, Brisbane, Queensland, Australia

    Jian Yang, Beben Benyamin, Brian P McEvoy, Scott Gordon, Anjali K Henders, Dale R Nyholt, Nicholas G Martin, Grant W Montgomery & Peter M Visscher

  2. Department of Psychiatry, Washington University, St. Louis, Missouri, USA

    Pamela A Madden & Andrew C Heath

  3. Department of Food and Agricultural Systems, University of Melbourne, Parkville, Victoria, Australia

    Michael E Goddard

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Contributions

P.M.V. and M.E.G. designed the study. J.Y. performed statistical analyses. B.B., B.P.M., A.K.H., D.R.N. and S.G. performed quality control analyses and prepared data. D.R.N., P.A.M., A.C.H. and N.G.M. contributed genotype and phenotype data. J.Y., G.W.M., M.E.G. and P.M.V. contributed to writing the paper.

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Correspondence to Peter M Visscher.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Tables 1 and 2 and Supplementary Note (PDF 742 kb)

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Yang, J., Benyamin, B., McEvoy, B. et al. Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42, 565–569 (2010). https://doi.org/10.1038/ng.608

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