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 (β = -0.029, 95% CI = -0.045 to -0.013, p = 3.63 × 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.