Causal association between inflammatory bowel disease and type 2 diabetes: a bidirectional two-sample Mendelian randomization study

Abstract

Abstract Background Previous observational studies have shown a paradoxical association between inflammatory bowel disease (IBD) and type 2 diabetes (T2DM), and the causal relationship between the two is unclear. Using a bidirectional two-sample Mendelian randomization (MR), we explored the causal connection between IBD and T2DM. Methods We obtained the datasets of IBD, UC, CD and T2DM from IEU genome-wide association study (GWAS) summary statistics and extracted genetic variants as instrumental variables for bidirectional two-sample MR. The main MR analysis methods are Inverse-variance weighted. Mendelian randomization-Egger (MR-Egger) and the weighted median as a complementary MR analysis method. Finally, heterogeneity tests, horizontal multiple validity tests, and the leave-one-out sensitivity analysis were used to evaluate the robustness of the study results. Results MR analysis results showed no causal connection between IBD (IVW OR = 1.017, 95%CI 0.981–1.053, p = 0.361), ulcerative colitis (UC) (IVW OR = 0.997, 95%CI 0.964–1.031, p = 0.864), Crohn’s disease (CD) (IVW OR = 1.018, 95%CI 0.986–1.052, p = 0.27) and T2DM. In addition, the results of the reverse MR analysis revealed no proof to support the risk of T2DM with the development of IBD (IVW OR = 1.049, 95%CI 0.898–1.225, p = 0.544), UC (IVW OR = 0.945, 95%CI 0.801–1.115, p = 0.501), and CD (IVW OR = 1.085, 95%CI 0.928–1.27, p = 0.307). Similar results were obtained for the complementary MR analysis method. The SNPs used in this study exhibited no conspicuous horizontal pleiotropy, and sensitivity analysis showed the robustness of the findings. Conclusion Our bidirectional two-sample MR results showed no evidence to support a causal connection between IBD, UC, CD and T2DM in the European population.