Exploring the causal inference of inflammatory bowel disease and ischemic stroke: a bidirectional two-sample Mendelian randomization study

Abstract

Growing evidence suggests inflammatory bowel disease (IBD) is linked to ischemic stroke (IS); however, the results are inconclusive. Therefore, it remains uncertain whether the association between IBD and IS is causal. Herein, we performed a bidirectional Mendelian randomization (MR) study to examine the causal association of IBD with IS. We obtained summary-level data for IBD and IS from several publicly released genome-wide association studies to conduct a two-sample bidirectional Mendelian randomization (MR) analysis. Herein, the inverse-variance weighted method was utilized as the primary approach. Then, we applied the weighted median and MR-Egger estimators for the follow-up sensitivity analyses. In addition, the MR-Egger intercept test was performed to detect the potential directional pleiotropy. Genetically predicted IBD was not causally associated with IS and IS subtypes (IS: OR = 0.99, 95% CI 0.98-1.01, p = 0.49; large artery atherosclerosis stroke: OR = 1.00, 95% CI: 0.96-1.05, p = 0.88; cardioembolic stroke: OR = 0.99, 95% CI 0.96-1.03, p = 0.75; small-vessel occlusion stroke: OR = 1.02, 95% CI 0.99-1.05, p = 0.16). Moreover, we did not find a significant causal effect of UC or CD on IS and IS subtypes. Furthermore, there was no significant association observed between IS and IBD in the reverse MR analysis. The estimates were consistent across sensitivity analyses. Our MR analysis does not support a bidirectional causal association between IBD and IS, despite observational studies reporting an association of IBD with IS.

Keywords: Bowel; Disease·ischemic; Genome-wide association study; Inflammatory; Randomization·causal; Relationship; Stroke·mendelian.