Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases: a two-sample Mendelian randomization study

AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, 2100 the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P =2.54x10(-7) ). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P =3.20x10(-5) ), keratitis (IVW: OR, 1.06; 95%CI, 1.02(-1).09; P =1.13x10(-3) ), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P =1.43x10(-4) ). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.