Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation

Background: Despite growing evidence indicating that patients with inflammatory bowel disease (IBD) have an increased risk of atrial fibrillation (AF), owing to the potential biases of confounding effects and reverse causation, the specific relationship between IBD and AF remains controversial. The aim of this study is to determine whether there is a causal effect of IBD on AF. Methods: A two-sample Mendelian randomization (MR) study was performed to evaluate the causal effect of IBD on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and traits of interest were obtained from independent consortia with European populations. The dataset of IBD was acquired from genome-wide association studies (GWAS), including more than 75,000 cases and controls. A GWAS with 60,620 AF cases and 970,216 controls was used to identify genetic variation underlying AF. The causal effect was estimated using the multiplicative random effects inverse-variance weighted method (IVW), followed by sensitivity analysis. Results: Using 81 SNPs, there was no evidence to suggest an association between genetically predicted IBD and risk of AF with multiplicative random-effects IVW MR analysis (odds ratio = 1.0000, 95% confidence interval: 0.9994 1.0005, p = 0.88). Conclusion: As opposed to current assumptions, no substantial evidence was found to support a causal role of IBD in the development of AF.