Does Chronic Intestinal Inflammation Promote Atrial Fibrillation: A Mendelian Randomization Study With Populations of European Ancestry

Background: Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC), and Crohn's disease (CD), has been reported to be associated with an increased risk of atrial fibrillation (AF). However, the causal role of the chronic intestinal inflammation (CII) in the development of AF remains controversial. We use Mendelian randomization (MR) analysis to explore the causal inference of CII on AF. Methods: A two-sample MR analysis was performed to estimate the potential causal effect of CII on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and phenotypes of CII were obtained from genome-wide association studies (GWAS) with cohorts of CD (n = 51,874), UC (n = 47,745), and IBD (n = 65,642) of European descent. The GWAS of 1,030,836 people of European ancestry, including 60,620 AF cases and 970,216 controls was collected to identify genetic variants underlying AF. The causal inference was estimated using the multiplicative random effects inverse-variance weighted method (IVW). The methods of MR-Egger, simple median, and weighted median were also employed to avoid the bias of pleiotropy effects. Results: Using three sets of SNPs (75 SNPs of CD, 60 SNPs of UC, and 95 SNPs of IBD), multiplicative random-effect IVW model estimated a universal null effect of CII on AF (CD: OR = 1.0059, 95% CI: 0.9900, 1.0220, p = 0.47; UC: OR = 1.0087, 95% CI: 0.9896, 1.0281, p = 0.38; IBD: OR = 1.0080, 95% CI: 0.9908, 1.0255, p = 0.37). Similar results were observed using the MR-Egger, simple median, weighted median methods. Conclusion: As opposing to the traditional observational studies, our two-sample MR analysis did not find enough evidence to support a causal role of either CD or UC in the development of AF.