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
22426310
TITLE
Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits.
ABSTRACT
We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.
DATE PUBLISHED
2012 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/08/19
accepted 2012/02/06
aheadofprint 2012/03/18
entrez 2012/03/20 06:00
pubmed 2012/03/20 06:00
medline 2012/05/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Yang J Yang Jian J Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Ferreira T Ferreira Teresa T
Morris AP Morris Andrew P AP
Medland SE Medland Sarah E SE
Genetic Investigation of ANthropometric Traits (GIANT) Consortium
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
Madden PA Madden Pamela A F PA
Heath AC Heath Andrew C AC
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Weedon MN Weedon Michael N MN
Loos RJ Loos Ruth J RJ
Frayling TM Frayling Timothy M TM
McCarthy MI McCarthy Mark I MI
Hirschhorn JN Hirschhorn Joel N JN
Goddard ME Goddard Michael E ME
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
VOLUME: 44
ISSUE: 4
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2012
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
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
AA014041 NIAAA NIH HHS United States
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
DA12854 NIDA NIH HHS United States
HHSN268200625226C PHS HHS United States
HHSN268201100005C NHLBI NIH HHS United States
HHSN268201100005C PHS HHS United States
HHSN268201100006C NHLBI NIH HHS United States
HHSN268201100006C PHS HHS United States
HHSN268201100007C NHLBI NIH HHS United States
HHSN268201100007C PHS HHS United States
HHSN268201100008C NHLBI NIH HHS United States
HHSN268201100008C PHS HHS United States
HHSN268201100009C NHLBI NIH HHS United States
HHSN268201100009C PHS HHS United States
HHSN268201100010C NHLBI NIH HHS United States
HHSN268201100010C PHS HHS United States
HHSN268201100011C NHLBI NIH HHS United States
HHSN268201100011C PHS HHS United States
HHSN268201100012C NHLBI NIH HHS United States
HHSN268201100012C PHS HHS United States
K05 AA017688 NIAAA NIH HHS United States
MC_U106188470 Medical Research Council United Kingdom
R01 AA007535 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 HL059367 NHLBI NIH HHS United States
R01 HL086694 NHLBI NIH HHS United States
R01 HL087641 NHLBI NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
R01HL59367 NHLBI NIH HHS United States
U01 HG004402 NHGRI NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
WT083270 Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Algorithms
Body Height
Body Mass Index
Case-Control Studies
Cyclin-Dependent Kinase Inhibitor p15 genetics
Data Interpretation, Statistical genetics
Diabetes Mellitus, Type 2 genetics
Genetic Loci genetics
Genetic Variation genetics
Genome, Human genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Linkage Disequilibrium genetics
Meta-Analysis as Topic genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CDKN2B protein, human
0 Cyclin-Dependent Kinase Inhibitor p15
OTHER ID's
OTHERID SOURCE
NIHMS439103 NLM
PMC3593158 NLM