Genomewide association analysis of coronary artery disease

Samani, Nilesh J., Erdmann, Jeanette, Hall, Alistair S., Hengstenberg, Christian, Mangino, Mangino, Mayer, Bjoern, Dixon, Richard J., Meitinger, Thomas, Braund, Peter, Wichmann, H. Erich, Barrett, Jennifer H., Konig, 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, Steven G., Strom, Tim M., Braenne, Ingrid, Gieger, Christian, Deloukas, Panos, Tobin, Martin D., Ziegler, Andreas, Thompson, John R., Schunkert, Heribert, for the WTCCC and the Cardiogenics Consortium, Bradbury, Linda A. and Brown, Matthew A. (2007) Genomewide association analysis of coronary artery disease. The New England Journal of Medicine, 357 5: 443-453. doi:10.1056/NEJMoa072366

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Author Samani, Nilesh J.
Erdmann, Jeanette
Hall, Alistair S.
Hengstenberg, Christian
Mangino, Mangino
Mayer, Bjoern
Dixon, Richard J.
Meitinger, Thomas
Braund, Peter
Wichmann, H. Erich
Barrett, Jennifer H.
Konig, 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, Steven G.
Strom, Tim M.
Braenne, Ingrid
Gieger, Christian
Deloukas, Panos
Tobin, Martin D.
Ziegler, Andreas
Thompson, John R.
Schunkert, Heribert
for the WTCCC and the Cardiogenics Consortium
Bradbury, Linda A.
Brown, Matthew A.
Title Genomewide association analysis of coronary artery disease
Journal name The New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
1533-4406
Publication date 2007-08-02
Sub-type Article (original research)
DOI 10.1056/NEJMoa072366
Open Access Status File (Publisher version)
Volume 357
Issue 5
Start page 443
End page 453
Total pages 11
Editor Drazen, J.M.
Place of publication Boston, MA, United States
Publisher Massachusetts Medical Society
Collection year 2008
Language eng
Subject C1
270207 Quantitative Genetics
780105 Biological sciences
11 Medical and Health Sciences
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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