Inflammatory bowel disease and white matter microstructure: A bidirectional Mendelian randomization study

Background: Observational studies have reported changes in the brain white matter (WM) microstructure in patients with inflammatory bowel disease (IBD); however, it remains uncertain whether the relationship between them is causative. The aim of this study is to reveal the potential causal relationship between IBD and WM microstructure through a bidirectional two-sample Mendelian randomization (MR) analysis. Methods: We extracted genome-wide association study (GWAS) summary statistics for IBD and WM microstructure from published GWASs. Two-sample MR analysis was conducted to explore the bidirectional causal associations between IBD and WM microstructure, followed by a series of sensitivity analyses to assess the robustness of the results. Results: Although forward MR analysis results showed no evidence of causality from microstructural WM to IBD, reverse MR showed that genetically predicted IBD, consisting of ulcerative colitis and Crohn's disease, has a significant causal effect on the orientation dispersion index (OD) of the right tapetum (beta = -0.029, 95% CI = -0.045 to -0.013, p = 3.63 x 10-4). Further sensitivity analysis confirmed the robustness of the association. Conclusion: Our results suggested the potentially causal association of IBD with reduced OD in the right tapetum.