University of Leicester
Browse
nejmoa072366.pdf (506.09 kB)

Genomewide Association Analysis of Coronary Artery Disease

Download (506.09 kB)
journal contribution
posted on 2009-12-09, 14:41 authored by Nilesh J. Samani, Jeanette Erdmann, Alistair S. Hall, Christian Hengstenberg, Massimo Mangino, Bjoern Mayer, Richard J. Dixon, Thomas Meitinger, Peter S. Braund, H.-Erich Wichmann, Jennifer H. Barrett, Inke R. König, Suzanne E. Stevens, Silke Szymczak, David-Alexandre Tregouet, Mark M. Iles, Friedrich Pahlke, Helen Pollard, Wolfgang Lieb, Francois Cambien, Marcus Fischer, Willem Ouwehand, Stefan Blankenberg, Anthony J. Balmforth, Andrea Baessler, Stephen G. Ball, Tim M. Strom, Ingrid Brænne, Christian Gieger, Panos Deloukas, Martin D. Tobin, Andreas Ziegler, John R. Thompson, Heribert Schunkert, Wellcome Trust Case Control Consortium, Cardiogenics Consortium
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.

History

Citation

New England Journal of Medicine, 2007, 357 (5), pp. 443-453.

Published in

New England Journal of Medicine

Publisher

Massachusetts Medical Society

issn

0028-4793

Copyright date

2007

Available date

2009-12-09

Publisher version

http://www.nejm.org/doi/full/10.1056/NEJMoa072366

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Keywords

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC