PMID |
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TITLE |
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Estimating missing heritability for disease from genome-wide association studies. |
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ABSTRACT |
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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. |
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2010/09/30 |
revised |
2010/12/10 |
accepted |
2011/02/01 |
aheadofprint |
2011/03/03 |
entrez |
2011/03/08 06:00 |
pubmed |
2011/03/08 06:00 |
medline |
2011/05/17 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Lee SH |
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Lee |
Sang Hong |
SH |
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Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia. |
Wray NR |
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Wray |
Naomi R |
NR |
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Goddard ME |
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Goddard |
Michael E |
ME |
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Visscher PM |
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Visscher |
Peter M |
PM |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 88 |
ISSUE: 3 |
TITLE: American journal of human genetics |
ISOABBREVIATION: Am. J. Hum. Genet. |
YEAR: 2011 |
MONTH: Mar |
DAY: 11 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1537-6605 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Am J Hum Genet |
COUNTRY: United States |
ISSNLINKING: 0002-9297 |
NLMUNIQUEID: 0370475 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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CommentIn |
Am J Hum Genet. 2011 Jul 15;89(1):191-3; author reply 193-5 |
21763486 |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
076113 |
Wellcome Trust |
United Kingdom |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Bipolar Disorder |
genetics |
Case-Control Studies |
genetics |
Computer Simulation |
genetics |
Crohn Disease |
genetics |
Diabetes Mellitus, Type 1 |
genetics |
Disease |
genetics |
Genetic Variation |
genetics |
Genome-Wide Association Study |
methods |
Humans |
methods |
Inheritance Patterns |
genetics |
Models, Genetic |
genetics |
Polymorphism, Single Nucleotide |
genetics |
Quality Control |
genetics |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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OTHERID |
SOURCE |
PMC3059431 |
NLM |
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