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 Mar 18
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/08/19
accepted 2012/02/06
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: Mar
DAY: 18
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
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
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites Hum Mol Genet. 2011 Oct 15;20(20):4082-92 21798870
Cites Twin Res. 2003 Oct;6(5):409-21 14624725
Cites Hum Mol Genet. 2004 Nov 1;13(21):2557-65 15367493
Cites Lancet. 1991 Aug 24;338(8765):464-8 1678444
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Nature. 2007 Oct 18;449(7164):851-61 17943122
Cites Nat Rev Genet. 2008 Apr;9(4):255-66 18319743
Cites Eur J Hum Genet. 2009 Jun;17(6):802-10 19127282
Cites Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 19474294
Cites Genome Res. 2009 Oct;19(10):1849-60 19541915
Cites Am J Hum Genet. 2009 Nov;85(5):750-5 19896111
Cites Nat Genet. 2010 Jun;42(6):504-7 20453838
Cites Nat Genet. 2010 Jul;42(7):565-9 20562875
Cites Nat Genet. 2011 Oct;43(10):977-83 21926972
Cites Nat Genet. 2011 Oct;43(10):969-76 21926974
Cites Nat Genet. 2011 Dec;43(12):1193-201 22057235
Cites Nat Genet. 2010 Jul;42(7):579-89 20581827
Cites N Engl J Med. 2010 Jul 8;363(2):166-76 20647212
Cites Genet Epidemiol. 2010 Sep;34(6):591-602 20718045
Cites Nature. 2010 Oct 14;467(7317):832-8 20881960
Cites Nat Genet. 2010 Nov;42(11):937-48 20935630
Cites Nature. 2010 Oct 28;467(7319):1061-73 20981092
Cites Genet Epidemiol. 2010 Dec;34(8):816-34 21058334
Cites Nat Genet. 2010 Dec;42(12):1049-51 21057501
Cites Genet Sel Evol. 2010;42:41 21092198
Cites Am J Hum Genet. 2011 Jan 7;88(1):76-82 21167468
Cites Nat Genet. 2011 Jun;43(6):519-25 21552263
Cites Eur J Hum Genet. 2011 Jul;19(7):807-12 21407268
Cites Nat Genet. 2011 Aug;43(8):801-5 21775993
Cites PLoS Genet. 2011 Jul;7(7):e1002198 21829380
Cites Int J Obes Relat Metab Disord. 2002 Sep;26(9):1225-31 12187400
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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
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