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

Purpose: This study aims to explore the relationship between autoimmune rheumatic diseases (ARDs) and the risk of iridocyclitis (IC) using Mendelian randomization (MR) analysis.

Methods: 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.

Results: 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.

Conclusion: 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.