Format

Send to

Choose Destination
See comment in PubMed Commons below
Circulation. 2008 Apr 1;117(13):1675-84. doi: 10.1161/CIRCULATIONAHA.107.730614. Epub 2008 Mar 24.

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

Author information

  • 1Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany. heribert.schunkert@innere2.uni-luebeck.de

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.

PMID:
18362232
PMCID:
PMC2689930
DOI:
10.1161/CIRCULATIONAHA.107.730614
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center