Cao Xiang, Xu Zijiao, Zhang Boyang, Jiang Zhixin, Yuan Xiaoyong
Department of Ophthalmology, Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, 212002, China.
Zhenjiang Kangfu Eye Hospital, Zhenjiang, Jiangsu, 212002, China.
Genes Nutr. 2025 Mar 28;20(1):8. doi: 10.1186/s12263-025-00767-8.
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.
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.
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.
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.
随着全球人口老龄化，老年性白内障（SC）、年龄相关性黄斑变性（AMD）、青光眼和糖尿病视网膜病变（DR）等年龄相关性眼病（AREDs）正日益成为重大的公共卫生问题。AREDs患病率的上升凸显了对有效预防和治疗策略的迫切需求。本研究旨在探讨循环微营养素（CMs）与AREDs之间的因果关系。
采用双向双样本孟德尔随机化（MR）分析，以基因变异作为工具变量，评估15种CMs（维生素A、维生素B6、维生素B12、维生素C、维生素D、维生素E、叶酸、胡萝卜素、铜、钙、铁、镁、钾、硒、锌）对AREDs的影响。数据来源于大规模全基因组关联研究（GWAS）。采用的主要分析方法是逆方差加权（IVW），并辅以敏感性分析以确认结果的稳健性。
MR分析显示，硒对SC（比值比[OR]=0.961，95%置信区间[CI]=0.932-0.991，P=0.012）和DR（OR=0.927，95%CI=0.870-0.987，P=0.019）具有显著的保护作用。此外，较高的遗传预测镁水平与AMD风险降低相关（OR=0.679，95%CI=0.515-0.895，P=0.006）。然而，未观察到其他CMs与青光眼或其他AREDs之间存在显著的因果关系。
这些发现为CMs与AREDs之间的复杂相互作用提供了有价值的见解，为制定有针对性的营养干预措施和公共卫生策略以降低这些使人衰弱疾病的风险提供了潜在途径。
