Abstract
Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR-Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 × 10-8) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 × 10-8) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 × 10-8) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships.
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