Causal Relationship Between Autoimmune Rheumatic Diseases and Iridocyclitis: A Bidirectional Two-Sample Mendelian Randomization Study

This study aims to explore the relationship between autoimmune rheumatic diseases (ARDs) and the risk of iridocyclitis (IC) using Mendelian randomization (MR) analysis. Data of ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), Behcet's disease (BD), and iridocyclitis were obtained from genome-wide association studies with large sample sizes. The instrumental variable utilized in this study for each exposure was the single nucleotide polymorphism. The inverse-variance weighted (IVW) method, which included random effects, was used to analyze causal effects. In addition, sensitivity analyses were conducted using the weighted median and MR-Egger methods. The presence of pleiotropic effects was identified and addressed through MR pleiotropic effects residual and outlier tests, as well as MR-Egger modeling. We found a causal effect of AS (IVW, OR = 2.74 × 1029, 95% CI 6.39 × 107 - 1.18 × 1051, p = 0.008) on IC. Conversely, we also found a causal effect of IC on AS (IVW OR = 1.01, 95% CI 1.00 - 1.01, p < 0.001). Besides, sensitivity analysis showed no evidence of pleiotropy and heterogeneity. However, no causal relationship between SLE, JIA, BD, and IC was detected. Bilateral causal relationships of IC and AS were identified, which could offer evidence for clinical use and lay the groundwork for detecting potential mechanism behind them.