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Schunkert, H.* ; Götz, A.* ; Braund, P.* ; McGinnis, R.* ; Tregouet, D.A.* ; Mangino, M.* ; Linsel-Nitschke, P.* ; Cambien, F.* ; Hengstenberg, C.* ; Stark, K.* ; Blankenberg, S.* ; Tiret, L.* ; Ducimetiere, P.* ; Keniry, A.* ; Ghori, M.J.* ; Schreiber, S.* ; El, Mokhtari, N.E.* ; Hall, A.S.* ; Dixon, R.J.* ; Goodall, A.H.* ; Liptau, H.* ; Pollard, H.* ; Schwarz, D.F.* ; Hothorn, L.A.* ; Wichmann, H.-E. ; König, I.R.* ; Fischer, M.* ; Meisinger, C. ; Ouwehand, W.* ; Deloukas, P.* ; Thompson, J.R.* ; Erdmann, J.* ; Ziegler, A.* ; Samani, N.J.* ; CARDIOGENICS Consortium (*)

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

Circulation 117, 1675-1684 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter chromosomes; coronary disease; genetics; meta-analysis; myocardial infarction; risk factors
ISSN (print) / ISBN 0009-7322
e-ISSN 1524-4539
Zeitschrift Circulation
Quellenangaben Band: 117, Heft: 13, Seiten: 1675-1684 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)