Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.

Schunkert, H; Götz, A; Braund, P; McGinnis, R; Trégouët, DA; Mangino, M; Linsel-Nitschke, P; Cambien, F; Hengstenberg, C; Stark, K; Blankenberg, S; Tiret, L; Ducimetiere, P; Keniry, A; Ghori, MJ; Schreiber, S; El Mokhtari, NE; Hall, AS; Dixon, RJ; Goodall, AH; Liptau, H; Pollard, H; Schwarz, DF; Hothorn, LA; Wichmann, HE; König, IR; Fischer, M; Meisinger, C; Ouwehand, W; Deloukas, P; Thompson, JR; Erdmann, J; Ziegler, A; Samani, NJ

doi:10.1161/CIRCULATIONAHA.107.730614

journal article

Document type:: Comparative Study; Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Article
Author(s):: Schunkert, H; Götz, A; Braund, P; McGinnis, R; Trégouët, DA; Mangino, M; Linsel-Nitschke, P; Cambien, F; Hengstenberg, C; Stark, K; Blankenberg, S; Tiret, L; Ducimetiere, P; Keniry, A; Ghori, MJ; Schreiber, S; El Mokhtari, NE; Hall, AS; Dixon, RJ; Goodall, AH; Liptau, H; Pollard, H; Schwarz, DF; Hothorn, LA; Wichmann, HE; König, IR; Fischer, M; Meisinger, C; Ouwehand, W; Deloukas, P; Thompson, JR; Erdmann, J; Ziegler, A; Samani, NJ
Title:: Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.
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=6.04x10(-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. CONCLUSIONS: This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.
Journal title abbreviation:: Circulation
Year:: 2008
Journal volume:: 117
Journal issue:: 13
Pages contribution:: 1675-84
Language:: eng
Fulltext / DOI:: doi:10.1161/CIRCULATIONAHA.107.730614
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/18362232
Print-ISSN:: 0009-7322
TUM Institution:: Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin
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mediaTUM Gesamtbestand Hochschulbibliographie 2008 Fakultäten Medizin Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin

mediaTUM Gesamtbestand Einrichtungen Schools und Fakultäten Fakultät für Medizin Kliniken und Institute Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin 2008