Journal article

Estimating Missing Heritability for Disease from Genome-wide Association Studies

Sang Hong Lee, Naomi R Wray, Michael E Goddard, Peter M Visscher

American Journal of Human Genetics | CELL PRESS | Published : 2011

Abstract

Genome-wide association studies are designed to discover SNPs that are associated with a complex trait. Employing strict significance thresholds when testing individual SNPs avoids false positives at the expense of increasing false negatives. Recently, we developed a method for quantitative traits that estimates the variation accounted for when fitting all SNPs simultaneously. Here we develop this method further for case-control studies. We use a linear mixed model for analysis of binary traits and transform the estimates to a liability scale by adjusting both for scale and for ascertainment of the case samples. We show by theory and simulation that the method is unbiased. We apply the metho..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council


Awarded by Australian Research Council


Awarded by Wellcome Trust


Awarded by Netherlands Scientific Organization


Funding Acknowledgements

We acknowledge funding from the Australian National Health and Medical Research Council (Grants 389892, 442915, 496688, 613672, and 613601) and the Australian Research Council (Grants DP0770096 and DP1093900 and Future Fellowship to N.R.W.). This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the WTCCC data is available from www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under award 076113. We thank Stuart Macgregor for useful discussions and suggestions. S.H.L. acknowledges the use of the Genetic Cluster Computer for carrying out simulations. The cluster is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). We thank the referees for many helpful comments and suggestions.