Background: Iridocyclitis (IC) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Observational studies showed patients with ulcerative colitis (UC) and Crohn's disease (CD) both have a higher risk of IC. However, due to the inherent limitations of observational studies, the association and its directionality between the two forms of IBD and IC remain undiscerned.
Methods: Genetic variants for IBD and IC were selected as instruments from genome-wide association studies (GWAS) and FinnGen database as instrumental variables, respectively. A bidirectional Mendelian randomization (MR) and multivariable MR were performed successively. Three different MR methods were performed to determine the causal association, including inverse-variance weighted (IVW), MR Egger, and weighted median, whereas IVW was used as the main analysis. Different methods for sensitivity analysis were used, including MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, Cochran's Q test, and leave-one-out analysis.
Results: Bidirectional MR suggested both UC and CD were positively associated with IC as a whole, acute and subacute IC, and chronic IC. However, in the MVMR analysis, only the association from CD to IC remained stable. In the reverse analysis, no association was observed from IC to UC or CD.
Conclusions: Both UC and CD are associated with an increased risk of IC compared with healthy individuals. However, the association between CD and IC is stronger. In the reverse direction, patients with IC do not suffer a higher risk of UC or CD. We emphasize the importance of ophthalmic examinations for IBD patients, especially for CD patients.
Keywords: Crohn’s disease; Mendelian randomization; inflammatory bowel disease; iridocyclitis; ulcerative colitis.