Genomewide Association Analysis of Coronary Artery Disease

作者：Nilesh J. Samani, Jeanette Erdmann, Alistair S. Hall, Christian Hengstenberg, Massimo Mangino, Bjoern Mayer, Richard J. Dixon, Thomas Meitinger, Peter S. Braund, H. E. Wichmann, Jennifer H. Barrett, Inke Regina König, Suzanne Stevens, Silke Szymczak, David‐Alexandre Trégouët, Mark Martin Iles, Friedrich Pahlke, Helen Perlstein Pollard, Wolfgang Lieb, François Cambien, Marcus Fischer, Willem Hendrik Ouwehand, Stefan Blankenberg, Anthony J. Balmforth, Andrea Baessler, Stephen G. Ball, Tim Matthias Strom, Ingrid Brænne, Christian Gieger, Panos Deloukas, Martin D. Tobin, Andreas Ziegler, John R. Thompson, Heribert Schunkert · 发表于：New England Journal of Medicine · 年份：2007 · DOI：10.1056/nejmoa072366 · 被引用次数：2059 · 研究领域：Genetic Associations and Epidemiology、Genomic variations and chromosomal abnormalities、Kruppel-like factors research

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 Ger...