Associations Between Serum Uric Acid Levels and Glaucoma: Results From the LifeLines Cohort and UK Biobank

Purpose: The purpose of this study was to investigate the association between serum uric acid (UA) levels and primary open-angle glaucoma (POAG), and to explore potential genetic links and causal relationships using large population-based cohorts. Methods: We analyzed data from 7443 participants in the LifeLines cohort and 90,107 participants in the UK Biobank, all aged ≥55 years. Glaucoma status was determined based on questionnaires and International Classification of Diseases (ICD) codes. Logistic regression was used to assess the association between serum UA levels and glaucoma, adjusting for demographic, clinical, and lifestyle covariates. Meta-analysis was performed to combine results across cohorts. Genetic correlation, polygenic risk score (PRS), and two-sample Mendelian randomization (MR) analyses were conducted to evaluate shared genetic architecture and causality. Results: Higher serum UA levels were significantly associated with increased odds of glaucoma in the UK Biobank (per 0.1 mM increase, odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.02-1.11, P = 0.007 in the fully adjusted model), with consistent findings in meta-analysis. No association was observed in the LifeLines cohort. Genetic analyses revealed no evidence of shared genetic correlation or causality between UA and glaucoma. The UA PRS was not associated with glaucoma odds, and the glaucoma PRS showed no association with serum UA levels. Conclusions: Elevated serum UA levels were phenotypically associated with glaucoma, but genetic analyses did not support a causal link. UA may reflect systemic oxidative stress rather than directly contribute to glaucoma pathogenesis. Further studies are needed to clarify underlying mechanisms and clinical relevance.