Association between 1p13.3 genomic markers and coronary artery disease: a meta-analysis involving patients and controls

Recently, genome-wide association studies on cardiovascular disease identified a series of associated single nucleotide polymorphisms in an intergenic region of chromosome 1p13.3. We investigated the association of this locus with cardiovascular disease in 13 case-control studies and undertook a meta-analysis for effect size, heterogeneity, publication bias, and strength of evidence. English and Chinese language articles were screened for the association of 1p13.3 single nucleotide polymorphisms with coronary heart/artery disease or myocardial infarction as primary outcomes. The included articles provided race, numbers of participants, and the data necessary to compute an odds ratio. Articles were excluded if other outcomes were reported or 1p13.3 single nucleotide polymorphisms were not included. Thirty-five articles were initially identified and 12 were eventually included in the meta-analysis. rs599839 and rs646776, representing the 1p13.3 locus, were genotyped in 13 case-control studies involving a total of 17,766 patients and 20,272 controls. For rs599839 (11 data sets), using a random-effect model, the summary odds ratio was 1.17 (95% con-fidence interval = 1.07-1.28, P = 0.0001). For rs646776 (4 data sets), using a fixed-effects model, the summary odds ratio was 1.13 (95% confidence interval = 1.06-1.21, P = 0.0001). This broad replication provided unprecedented evidence for an association between genetic variants at chromosome 1p13.3 and the risk of cardiovascular disease.