Estimating missing heritability for disease from genome-wide association studies

Lee, Sang Hong, Wray, Naomi R., Goddard, Michael E. and Visscher, Peter M. (2011) Estimating missing heritability for disease from genome-wide association studies. American Journal of Human Genetics, 88 3: 294-305. doi:10.1016/j.ajhg.2011.02.002

Author Lee, Sang Hong
Wray, Naomi R.
Goddard, Michael E.
Visscher, Peter M.
Title Estimating missing heritability for disease from genome-wide association studies
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2011-03
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2011.02.002
Volume 88
Issue 3
Start page 294
End page 305
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
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 method to data from the Wellcome Trust Case Control Consortium and show that a substantial proportion of variation in liability for Crohn disease, bipolar disorder, and type I diabetes is tagged by common SNPs.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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