Abstract 13656: Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: the CHARGE Consortium
Background: Previous genome-wide association (GWA) studies identified multiple genetic loci for myocardial infarction (MI) and coronary heart disease (CHD), using mainly case-control studies. Data are limited on GWA studies for CHD in prospective, population-based cohorts. Moreover, it is unclear if the gene variants identified to date also associate with risk of CHD in a prospective setting.
Methods: We performed a genome wide association (GWA) meta-analysis of the association of 2.5 million SNPs (HapMap imputation) with incident MI and CHD in 24,024 participants from five prospective cohort studies (including 1570 cases of MI, 2406 cases of CHD). We took suggestive SNPs to stage II and conducted association studies for further validation in a panel of seven prospective studies comprising 40,273 individuals (including 2328 cases of MI, 3059 cases of CHD).
Results: In Stage I, SNPs passed a discovery threshold of 5х10-6 in 8 loci for MI and 8 loci for CHD, of which one locus overlapped. We took 60 SNPs representing these 15 loci to stage II. All four SNPs close to QKI showed nominally significant association with MI (p-value<0.034) in Stage II and three of them exceeded genome-wide significant threshold when stage I and stage II results were combined (rs6941513 [G]: Hazard Ratio = 1.22 [95% Confidence Interval: 1.13 - 1.31]; p=6.2х10-9). While QKI has not been previously described to be associated with MI or CHD, 10 out of 46 SNPs known to be associated with coronary artery disease from previous GWA case-control studies showed modest evidence for association. Finally, a genotype score composed of these known SNPs was associated with the incidence of MI (p-value for association) and CHD (p-value for association) in our prospective setting.
Conclusions: SNPs in the QKI locus predict the incidence of cardiovascular disease in prospective studies. In our study we found different genetic loci that contribute to the risk of incident cardiovascular disease in a prospective setting compared to those found in prior case-control studies.
- © 2013 by American Heart Association, Inc.