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Inflammatory bowel disease and white matter microstructure: A bidirectional Mendelian randomization study
Jie Yu1, Wanyu Xie1, Ping Wang1
1School of Medical Technology, School of Medical Imaging, Tianjin Medical University, Tianjin, China.
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.
Insights
Inflammatory bowel disease (IBD) may causally affect white matter microstructure, specifically reducing the orientation dispersion index (OD) in the right tapetum. This Mendelian randomization study suggests a potential link between IBD and brain changes.
Area of Science:
- Neuroscience
- Gastroenterology
- Genetics
Background:
- Observational studies suggest altered brain white matter (WM) microstructure in inflammatory bowel disease (IBD) patients.
- Causality between IBD and WM microstructure changes remains uncertain.
Purpose of the Study:
- To investigate the potential causal relationship between IBD and WM microstructure.
- Utilize bidirectional two-sample Mendelian randomization (MR) analysis.
Main Methods:
- Extracted genome-wide association study (GWAS) summary statistics for IBD and WM microstructure.
- Performed bidirectional two-sample MR analysis.
- Conducted sensitivity analyses to ensure result robustness.
Main Results:
- No evidence of causality from WM microstructure to IBD was found.
- Genetically predicted IBD (ulcerative colitis and Crohn's disease) showed a significant causal effect on the orientation dispersion index (OD) of the right tapetum (β = -0.029, p = 3.63 × 10⁻⁴).
- Sensitivity analyses confirmed the association's robustness.
Conclusions:
- IBD is potentially associated with reduced OD in the right tapetum.
- Suggests a causal link between inflammatory bowel disease and specific white matter alterations.
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