Association between iridocyclitis and immune-related disease: A 2-sample Mendelian randomization study

The genetic basis of iridocyclitis, an inflammatory eye disease, remains poorly understood, particularly in relation to autoimmune diseases. This study aimed to explore the causal associations between 6 immune-related diseases and iridocyclitis using Mendelian randomization (MR). A total of 230 single nucleotide polymorphisms (SNPs) significantly associated with systemic lupus erythematosus, ankylosing spondylitis (AS), rheumatoid arthritis (RA), Graves disease (GD), Crohn disease (CD), and allergic contact dermatitis were identified based on stringent MR assumptions. These SNPs served as instrumental variables to estimate the causal effect of each autoimmune disease on iridocyclitis risk. The analysis utilized the inverse variance weighted method, complemented by sensitivity analyses including MR-Egger regression and leave-one-out testing to assess pleiotropy and robustness. The MR analysis revealed significant associations between genetically predicted AS (odds ratio [OR]: 1.544, 95% confidence interval [CI]: 1.494-1.595, P = 1.99 × 10-226), RA (OR: 1.207, 95% CI: 1.052-1.385, P = .003), and CD (OR: 1.654, 95% CI: 1.263-2.166, P = 2.54 × 10⁻⁶) with an increased risk of iridocyclitis. Conversely, higher genetically predicted GD was associated with a decreased risk of iridocyclitis (OR: 0.763, 95% CI: 0.674-0.865, P = .0002). Although systemic lupus erythematosus and allergic contact dermatitis appeared to have a protective effect, these results were not statistically significant, and no causal relationship could be established. Heterogeneity was observed among the SNPs, but no significant horizontal pleiotropy was detected. This study identifies potential genetic links between AS, RA, CD, GD, and the risk of iridocyclitis, providing new insights into the genetic underpinnings of this eye disease. The results support the need for further investigation into the genetic and molecular mechanisms underlying these associations.