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
21407268
TITLE
Genomic inflation factors under polygenic inheritance.
ABSTRACT
Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and 'genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of ~4000 and ~133,000 individuals.
DATE PUBLISHED
2011 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/03/16
entrez 2011/03/17 06:00
pubmed 2011/03/17 06:00
medline 2011/10/06 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Yang J Yang Jian J Queensland Statistical Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. jian.yang@qimr.edu.au
Weedon MN Weedon Michael N MN
Purcell S Purcell Shaun S
Lettre G Lettre Guillaume G
Estrada K Estrada Karol K
Willer CJ Willer Cristen J CJ
Smith AV Smith Albert V AV
Ingelsson E Ingelsson Erik E
O'Connell JR O'Connell Jeffrey R JR
Mangino M Mangino Massimo M
Mägi R Mägi Reedik R
Madden PA Madden Pamela A PA
Heath AC Heath Andrew C AC
Nyholt DR Nyholt Dale R DR
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Frayling TM Frayling Timothy M TM
Hirschhorn JN Hirschhorn Joel N JN
McCarthy MI McCarthy Mark I MI
Goddard ME Goddard Michael E ME
Visscher PM Visscher Peter M PM
GIANT Consortium
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 7
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2011
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5438
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
DA12854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Computer Simulation
Genome genetics
Genome-Wide Association Study genetics
Humans genetics
Models, Genetic genetics
Multifactorial Inheritance genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3137506 NLM