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Title: Genomewide Association Analysis of Coronary Artery Disease
Authors: Samani, Nilesh J.
Erdmann, Jeanette
Hall, Alistair S.
Hengstenberg, Christian
Mangino, Massimo
Mayer, Bjoern
Dixon, Richard J.
Meitinger, Thomas
Braund, Peter S.
Wichmann, H.-Erich
Barrett, Jennifer H.
König, Inke R.
Stevens, Suzanne E.
Szymczak, Silke
Tregouet, David-Alexandre
Iles, Mark M.
Pahlke, Friedrich
Pollard, Helen
Lieb, Wolfgang
Cambien, Francois
Fischer, Marcus
Ouwehand, Willem
Blankenberg, Stefan
Balmforth, Anthony J.
Baessler, Andrea
Ball, Stephen G.
Strom, Tim M.
Brænne, Ingrid
Gieger, Christian
Deloukas, Panos
Tobin, Martin D.
Ziegler, Andreas
Thompson, John R.
Schunkert, Heribert
Wellcome Trust Case Control Consortium
Cardiogenics Consortium
First Published: 2-Aug-2007
Publisher: Massachusetts Medical Society
Citation: New England Journal of Medicine, 2007, 357 (5), pp. 443-453.
Abstract: Background - Modern genotyping platforms permit a systematic search for inherited components of complex diseases. We performed a joint analysis of two genomewide association studies of coronary artery disease. Methods - We first identified chromosomal loci that were strongly associated with coronary artery disease in the Wellcome Trust Case Control Consortium (WTCCC) study (which involved 1926 case subjects with coronary artery disease and 2938 controls) and looked for replication in the German MI [Myocardial Infarction] Family Study (which involved 875 case subjects with myocardial infarction and 1644 controls). Data on other single-nucleotide polymorphisms (SNPs) that were significantly associated with coronary artery disease in either study (P<0.001) were then combined to identify additional loci with a high probability of true association. Genotyping in both studies was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). Results - Of thousands of chromosomal loci studied, the same locus had the strongest association with coronary artery disease in both the WTCCC and the German studies: chromosome 9p21.3 (SNP, rs1333049) (P=1.80x10–14 and P=3.40x10–6, respectively). Overall, the WTCCC study revealed nine loci that were strongly associated with coronary artery disease (P<1.2x10–5 and less than a 50% chance of being falsely positive). In addition to chromosome 9p21.3, two of these loci were successfully replicated (adjusted P<0.05) in the German study: chromosome 6q25.1 (rs6922269) and chromosome 2q36.3 (rs2943634). The combined analysis of the two studies identified four additional loci significantly associated with coronary artery disease (P<1.3x10–6) and a high probability (>80%) of a true association: chromosomes 1p13.3 (rs599839), 1q41 (rs17465637), 10q11.21 (rs501120), and 15q22.33 (rs17228212). Conclusions - We identified several genetic loci that, individually and in aggregate, substantially affect the risk of development of coronary artery disease.
DOI Link: 10.1056/NEJMoa072366
ISSN: 0028-4793
Type: Article
Rights: This paper was published as New England Journal of Medicine, 2007, 357 (5), pp. 443-453. Copyright © 2007 Massachusetts Medical Society. It is available from Doi: 10.1056/NEJMoa072366 Archived with reference to SHERPA/RoMEO and publisher website.
Appears in Collections:Published Articles, Dept. of Health Sciences

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