Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21376301
TITLE
Estimating missing heritability for disease from genome-wide association studies.
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.
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2011 Mar 11
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lee SH Lee Sang Hong SH Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia.
Wray NR Wray Naomi R NR
Goddard ME Goddard Michael E ME
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
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
GRANTS
GRANTID AGENCY COUNTRY
076113 Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
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
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3059431 NLM