Inflammatory Bowel Disease and Risk of Ocular Inflammation: A Two-sample Mendelian Randomization Study

Abstract

Purpose: To determine whether there is a causal effect of inflammatory bowel disease (IBD) on ocular inflammation? Design: Two-sample Mendelian randomization (MR) study. Methods: IBD-associated genetic instruments were derived from the largest genome-wide association studies published to date for IBD, ulcerative colitis (UC), and Crohn’s diseases (CD). FinnGen research project was used to identify genetic risk variants for conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Inverse-variance−weighted (IVW) was used as the primary outcome, while weighted median (WM) and MR-Egger were used to improve the estimation of IVW. Results: A nominal causal effect of genetically predicted IBD on risk of conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, 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=2.54×10-7), CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95% CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95% CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95% CI, 1.04-1.14; P=1.43×10-4). Conclusion: This study illustrates that IBD causally poses a risk of inflammation of conjunctival, cornea, iris-ciliary，and optic neuritis. Moreover, CD is more closely associated with the eye than UC. These implyed that the relationship of IBD and different parts of the eye structure were different, and provided novel evidence linking based on the association of the gut-eye axis.

Genome-wide association study of anterior uveitis

“…3 Anterior uveitis has been shown to co-occur with autoimmune diseases including spondyloarthropathies such as ankylosing spondylitis and psoriatic arthritis, and also with inflammatory bowel disease, juvenile idiopathic arthritis and tubulointerstitial nephritis. [4][5][6][7] The association of anterior uveitis with human leukocyte antigen (HLA)-B27 is well-established. 8 Various genes have been associated with anterior uveitis in previous small-scale association studies, including immune-related genes such as those in the HLA region (HLA-B, MICA) and others including CHF and C2, CYP27B1, KIR, and genes from the tumor-necrosis factor family and interleukin-1 families.…”