Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study

Area of Science:

• Ophthalmology
• Gastroenterology
• Genetics

Background:

• Iridocyclitis (IC) is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD).
• Observational studies suggest links between ulcerative colitis (UC), Crohn's disease (CD), and IC, but causality is unclear.

Purpose of the Study:

• To investigate the causal relationship between IBD subtypes (UC and CD) and IC using a bidirectional Mendelian randomization approach.
• To determine the directionality of the association between IBD and IC.

Main Methods:

• Utilized genetic variants from genome-wide association studies and the FinnGen database as instrumental variables.
• Performed bidirectional and multivariable Mendelian randomization (MR) analyses, employing inverse-variance weighted (IVW), MR Egger, and weighted median methods.
• Conducted sensitivity analyses including MR-Egger intercept, MR-PRESSO, Cochran's Q test, and leave-one-out analysis to ensure robustness.

Main Results:

• Bidirectional MR indicated positive associations between both UC and CD with IC (acute, subacute, and chronic).
• Multivariable MR confirmed a stable association from Crohn's disease (CD) to iridocyclitis (IC).
• Reverse analysis showed no causal association from IC to UC or CD.

Conclusions:

• Both UC and CD are associated with an elevated risk of IC, with CD exhibiting a stronger association.
• IC does not appear to increase the risk of developing UC or CD.
• Ophthalmic screening is crucial for IBD patients, particularly those with CD.