Schunkert, Heribert and Goetz, Anika and Braund, Peter and McGinnis, Ralph and Tregouet, David-Alexandre and Mangino, Massimo and Linsel-Nitschke, Patrick and Cambien, Francois and Hengstenberg, Christian and Stark, Klaus and Blankenberg, Stefan and Tiret, Laurence and Ducimetiere, Pierre and Keniry, Andrew and Ghori, Mohammed J. R. and Schreiber, Stefan and El Mokhtari, Nour Eddine and Hall, Alistair S. and Dixon, Richard J. and Goodall, Alison H. and Liptau, Henrike and Pollard, Helen and Schwarz, Daniel F. and Hothorn, Ludwig A. and Wichmann, H. -Erich and Koenig, Inke R. and Fischer, Marcus and Meisinger, Christa and Ouwehand, Willem and Deloukas, Panos and Thompson, John R. and Erdmann, Jeanette and Ziegler, Andreas and Samani, Nilesh J. (2008) Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. CIRCULATION, 117 (13). pp. 1675-1684. ISSN 0009-7322, 1524-4539
Full text not available from this repository. (Request a copy)Abstract
Background - Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis. Methods and Results - A single-nucleotide polymorphism (SNP), rs1333049, representing the 9p21.3 locus, was genotyped in 7 case-control studies involving a total of 4645 patients with myocardial infarction or CAD and 5177 controls. The mode of inheritance was determined. In addition, in 5 of the 7 studies, we genotyped 3 additional SNPs to assess a risk-associated haplotype (ACAC). Finally, a meta-analysis of the present data and previously published samples was conducted. A limited fine mapping of the locus was performed. The risk allele (C) of the lead SNP, rs1333049, was uniformly associated with CAD in each study (P < 0.05). In a pooled analysis, the odds ratio per copy of the risk allele was 1.29 (95% confidence interval, 1.22 to 1.37; P = 0.0001). Haplotype analysis further suggested that this effect was not homogeneous across the haplotypic background (test for interaction, P = 0.0079). An autosomal-additive mode of inheritance best explained the underlying association. The meta-analysis of the rs1333049 SNP in 12 004 cases and 28 949 controls increased the overall level of evidence for association with CAD to P = 6.04 x 10(-10) (odds ratio, 1.24; 95% confidence interval, 1.20 to 1.29). Genotyping of 31 additional SNPs in the region identified several with a highly significant association with CAD, but none had predictive information beyond that of the rs1333049 SNP. Conclusion - This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYOCARDIAL-INFARCTION; HEART-DISEASE; RISK-FACTORS; GENE; HAPLOTYPES; GENOME; chromosomes; coronary disease; genetics; meta-analysis; myocardial infarction; risk factors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Nov 2020 14:03 |
| Last Modified: | 04 Nov 2020 14:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31078 |
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