TY - JOUR
T1 - Genomewide association analysis of coronary artery disease
AU - Samani, Nilesh J.
AU - Erdmann, Jeanette
AU - Hall, Alistair S.
AU - Hengstenberg, Christian
AU - Mangino, Massimo
AU - Mayer, Bjoern
AU - Dixon, Richard J.
AU - Meitinger, Thomas
AU - Braund, Peter
AU - Wichmann, H. Erich
AU - Barrett, Jennifer H.
AU - König, Inke R.
AU - Stevens, Suzanne E.
AU - Szymczak, Silke
AU - Tregouet, David Alexandre
AU - Iles, Mark M.
AU - Pahlke, Friedrich
AU - Pollard, Helen
AU - Lieb, Wolfgang
AU - Cambien, Francois
AU - Fischer, Marcus
AU - Ouwehand, Willem
AU - Blankenberg, Stefan
AU - Balmforth, Anthony J.
AU - Baessler, Andrea
AU - Ball, Stephen G.
AU - Strom, Tim M.
AU - Brænne, Ingrid
AU - Gieger, Christian
AU - Deloukas, Panos
AU - Tobin, Martin D.
AU - Ziegler, Andreas
AU - Thompson, John R.
AU - Schunkert, Heribert
PY - 2007/8/2
Y1 - 2007/8/2
N2 - 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 = 1.80×10-14 and P = 3.40×10-6, respectively). Overall, the WTCCC study revealed nine loci that were strongly associated with coronary artery disease (P<1.2×10-5 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<1.3×10-6) 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.
AB - 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 = 1.80×10-14 and P = 3.40×10-6, respectively). Overall, the WTCCC study revealed nine loci that were strongly associated with coronary artery disease (P<1.2×10-5 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<1.3×10-6) 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.
UR - http://www.scopus.com/inward/record.url?scp=34547623750&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa072366
DO - 10.1056/NEJMoa072366
M3 - Journal articles
AN - SCOPUS:34547623750
SN - 0028-4793
VL - 357
SP - 443
EP - 453
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 5
ER -
