Abstract 18993: Genetic Variants Primarily Associated With Inflammatory Bowel Disease Do Not Associate With Coronary Artery Disease
Background: Patients suffering from inflammatory bowel disease (IBD) are at an increased risk for coronary artery disease (CAD). Despite the evident coincidence of these inflammatory conditions, a causal role of IBD for CAD has never been proven. Recently, many single nucleotide polymorphisms (SNPs) affecting IBD risk have been identified by genome-wide association studies (GWAS). If IBD acts as a causal trigger for CAD, one might expect that the IBD-associated SNPs alter the risk of CAD.
Methods and Results: We identified a total of 163 SNPs in the literature associated with IBD at a genome-wide significant level of p<5x10-8 and tested these for association with CAD in CARDIoGRAM, a meta-analytical dataset containing GWAS data from 22,233 CAD cases and 64,762 controls. Out of 147 SNPs, which passed quality control in CARDIoGRAM, 99 SNPs affected risk of ulcerative colitis (UC) and Crohn`s disease (CD) with consistent directionality. Approximately equal numbers of these IBD risk alleles produced odds ratios (ORs) for CAD greater (n=40) and smaller (n=59) than OR=1.0, consistent with no association between IBD-SNPs and CAD. Similar results were obtained by analyzing SNPs which only associate with either UC or CD. In total, 20 of the 147 SNPs are associated exclusively with UC and 28 are associated exclusively with CD, but not with UC. Neither UC- nor CD-associated risk alleles showed a positive association with CAD, i.e. the distribution of ORs for CAD above and below 1.0 was similar. Two UC-associated SNPs (rs4722672 and rs17229285) and four CD-associated SNPs (rs6679677, rs10061469, rs2024092, rs6651252) produced p-values below the 5-percent level with inconsistent directionality, none was study-wide significantly associated with CAD.
By contrast, blood pressure- (21 of 25 SNPs) and LDL cholesterol-associated SNPs (18 of 24 SNPs) increased CAD risk consistently to their effects on the underlying risk factors (OR>1, p=0.0008 and p=0.03, respectively).
Conclusion: Analyzing genetic information for the association of IBD and CAD, we found no evidence for a causal role of IBD in the pathogenesis of CAD. Rather, shared non-genetic factors might contribute to the coincidence of IBD and CAD.
Author Disclosures: H. Jansen: None. W. Lieb: None. P.G. Ferrario: None. N.P. Christopher: None. S. Kathiresan: None. R.P. Mudedach: None. T.L. Assimes: None. E. Boerwinkle: None. A.S. Hall: None. C. Hengstenberg: None. R. McPherson: None. R. Roberts: None. N.J. Samani: None. J. Erdmann: None. H. Schunkert: None.
- © 2014 by American Heart Association, Inc.