Causal relationship between air pollution and rheumatoid arthritis: A two-sample Mendelian randomization study

Recent studies have highlighted potential links between air pollution and autoimmune diseases. However, the causal relationship between air pollution (including PM2.5, PM10, nitrogen dioxide, and nitrogen oxides) and rheumatoid arthritis (RA) remains unclear. To address this, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal effects of air pollution on RA. Genome-wide association study data for air pollution metrics were utilized as exposures, while RA outcome data were sourced from European cohorts. Inverse variance weighting served as the primary method for causal estimation, supplemented by sensitivity analyses including weighted median, MR-Egger, weighted mode, and Bayesian weighted MR. All analyses were conducted using R software. Results from the inverse variance weighting method indicated no significant causal association between PM2.5 (odds ratio [OR] = 0.71, P = .183, 95% confidence interval [CI]: 0.27-1.91), PM10 (OR = 0.657, P = .143, 95% CI: 0.374-1.154), nitrogen dioxide (OR = 0.482, P = .163, 95% CI: 0.173-1.343), or nitrogen oxides (OR = 0.868, P = .782, 95% CI: 0.317-2.373), and RA risk. Sensitivity analyses confirmed robustness with no evidence of pleiotropy or heterogeneity (P > .05). This study provides the first MR evidence suggesting that air pollution may not exert a genetically predicted causal effect on RA, offering critical insights for public health strategies and future research on environmental triggers of autoimmune diseases.