ABSTRACT
BACKGROUND: The relationships between 25-hydroxyvitamin D [25(OH)D] and calcium and age-related macular degeneration (AMD) are unclear. OBJECTIVES: This study aimed to investigate the causal role of 25(OH)D concentrations, calcium concentrations, and dietary supplements use of vitamin D and calcium on risk of AMD and its subtypes. METHODS: Independent genetic variants associated with 25(OH)D and calcium concentrations were used as instrumental variables in published genome-wide association studies (GWASs) of European ancestry. The bidirectional 2-sample Mendelian randomization (MR) analyses were performed using summary-level data from the UK Biobank and FinnGen datasets. Sensitivity analyses were conducted to ensure the robustness of the MR results. The meta-analyses were conducted using both fixed-effect and random-effect models to provide comprehensive and reliable estimates. RESULTS: A standard deviation increase in calcium concentrations was linked to a 14%, 17%, and 13% reduction in the likelihood of developing AMD (95% confidence interval [CI]: 0.77, 0.97), wet AMD (95% CI: 0.73, 0.95), and dry AMD (95% CI: 0.75, 1.00), respectively. No significant causal relationships were detected between genetically predicted 25(OH)D concentrations and AMD and its subtypes (all P > 0.05). The combined analyses showed that higher calcium concentrations were associated with a reduced risk of overall AMD, with an odds ratio of 0.89 (95% CI: 0.81, 0.98). CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.
