Abstract
BACKGROUND: With the global population aging, age-related eye diseases (AREDs) such as senile cataract (SC), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are becoming increasingly significant public health concerns. The rising prevalence of AREDs underscores the urgent need for effective prevention and treatment strategies. This study aimed to explore the causal relationships between circulating micronutrients (CMs) and AREDs. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using genetic variants as instrumental variables to assess the effects of fifteen CMs (vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, folate, carotene, copper, calcium, iron, magnesium, potassium, selenium, zinc) on AREDs. Data were sourced from large-scale genome-wide association studies (GWAS). The primary analytical method employed was inverse-variance weighted (IVW), supplemented by sensitivity analyses to confirm the robustness of the results. RESULTS: The MR analysis revealed significant protective effects of selenium against SC (OR = 0.961, 95% CI = 0.932-0.991, P = 0.012) and DR (OR = 0.927, 95% CI = 0.870-0.987, P = 0.019). Furthermore, higher genetically predicted magnesium levels were associated with a reduced risk of AMD (OR = 0.679, 95% CI = 0.515-0.895, P = 0.006). However, no significant causal relationships were observed between the other CMs and glaucoma or other AREDs. CONCLUSIONS: These findings provided valuable insights into the complex interplay between CMs and AREDs, offering potential pathways for developing targeted nutritional interventions and public health strategies to mitigate the risk of these debilitating conditions.