Document Detail

Estimating missing heritability for disease from genome-wide association studies.
MedLine Citation:
PMID:  21376301     Owner:  NLM     Status:  MEDLINE    
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.
Sang Hong Lee; Naomi R Wray; Michael E Goddard; Peter M Visscher
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-03
Journal Detail:
Title:  American journal of human genetics     Volume:  88     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-05-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  294-305     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia.
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MeSH Terms
Bipolar Disorder / genetics
Case-Control Studies
Computer Simulation
Crohn Disease / genetics
Diabetes Mellitus, Type 1 / genetics
Disease / genetics*
Genetic Variation
Genome-Wide Association Study / methods*
Inheritance Patterns / genetics*
Models, Genetic
Polymorphism, Single Nucleotide / genetics
Quality Control
Grant Support
076113//Wellcome Trust
Comment In:
Am J Hum Genet. 2011 Jul 15;89(1):191-3; author reply 193-5   [PMID:  21763486 ]

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