Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study

Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran's Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results. Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019-1.064; P = 2.08×10-4) and glaucoma (OR = 1.029, 95% CI = 1.003-1.057; P = 2.94×10-2) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004-1.039; P = 1.64×10-2) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable. This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases.