Abstract
PURPOSE: Depression and glaucoma are globally prevalent disorders with emerging evidence suggesting a potential inter-relation. This study aims to gain an in-depth understanding of their association and shared mechanisms. METHODS: We investigated the association between depression and glaucoma using data from 348,537 Caucasian patients in the UK Biobank, including 7544 with glaucoma and 22,153 with depression. We performed Cox regression, logistic regression, mediation analyses, genetic association analysis, and Mendelian randomization. RESULTS: Logistic regression indicated that depression increased the odds of glaucoma by 1.63 times (95% confidence interval [CI] = 1.51-1.77) and glaucoma increased the odds of depression by 1.61 times (95% CI = 1.49-1.74). Cox regression showed a hazard ratio of 1.35 for glaucoma incidence in individuals with depression (95% CI = 1.07-1.70). The risk of glaucoma was consistently approximately 60% higher across various genetic components of depression. We examined 1463 protein markers, identifying 200 markers associated with depression, some of which are linked to lipid metabolism. Mediation analysis suggested lipid metabolism as a mediator among these two diseases, with proteins like ANPEP, CCL3, and VWA1 playing significant roles. Genetic correlation analysis revealed a substantial genetic connection among depression, glaucoma, and lipid metabolism traits. CONCLUSIONS: Significant associations between depression and glaucoma were observed, with lipid metabolism playing a crucial role in their diagnosis and treatment. TRANSLATIONAL RELEVANCE: Our research underscores the inter-relation between glaucoma and depression, highlighting the importance of lipid metabolism in their clinical management.