Inflammatory bowel disease and risk of coronary heart disease : A Mendelian randomization study

Abstract

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has been reported to be associated with an increased risk of coronary heart disease (CHD); however, the causal link between IBD and CHD is unclear. We performed Mendelian randomization (MR) analysis to investigate the association between genetically predicted IBD and CHD risk.

Methods: Exposure summary data were obtained from genome-wide association studies (GWAS) with cohorts of IBD (12,882 cases and 21,770 controls), UC (6968 cases and 20,464 controls), and CD (5956 cases and 14,927 controls) of European descent to identify single nucleotide polymorphisms (SNPs) as instrumental variables. Outcome summary data were obtained from a meta-analysis of 22 GWAS including 22,233 cases and 64,762 controls of European descent. To estimate MR, four methods were used, including inverse variance-weighted (IVW), MR-Egger, simple mode, and weighted median methods. Sensitivity analysis was also performed. The Bonferroni method was used to correct the bias of multiple testing.

Results: Three sets of SNPs (69 SNPs of IBD, 40 SNPs of UC, and 58 SNPs of CD) were used to estimate the causal effect between genetically predicted IBD and CHD. Using the IVW method, we found that no causal relationship between genetically predicted IBD and CHD after Bonferroni correction, and there was no causal relationship between UC/CD and the development of CHD. No evidence of significant heterogeneity and pleiotropy was found.

Conclusion: The results of this study suggested that genetically predicted IBD may have no causal effect on CHD risk in a population with European ancestry.

Keywords: Causal link; Crohn’s disease; Genome-wide association study; Single nucleotide polymorphisms; Ulcerative colitis.