Abstract：
BACKGROUND: The relationships between 25-hydroxyvitamin D (25(OH)D) and calcium and age-related macular degeneration (AMD) are unclear.
OBJECTIVE: 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 the 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 two-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 OR of 0.89 (95% CI = 0.81, 0.98).
CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and the risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.
OBJECTIVE: 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 the 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 two-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 OR of 0.89 (95% CI = 0.81, 0.98).
CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and the risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.
摘要：
背景：25-羟基维生素D（25（OH）D）和钙与年龄相关性黄斑变性（AMD）之间的关系尚不清楚。
目的：本研究旨在探讨25(OH)D浓度的因果关系。钙浓度，和膳食补充剂使用维生素D和钙对AMD及其亚型的风险。
方法：在已发表的欧洲血统全基因组关联研究（GWAS）中，将与25（OH）D和钙浓度相关的独立遗传变异用作工具变量。使用UKBiobank和FinnGen数据集的汇总数据进行双向双样本孟德尔随机化（MR）分析。进行敏感性分析以确保MR结果的稳健性。使用固定效应和随机效应模型进行荟萃分析，以提供全面可靠的估计。
结果：钙浓度的标准偏差增加与14%有关，17%,发生AMD的可能性降低13%(95%置信区间[CI]=0.77，0.97)，湿性AMD（95%CI=0.73，0.95），和干性AMD（95%CI=0.75，1.00），分别。基因预测的25(OH)D浓度与AMD及其亚型之间没有显著的因果关系(均P>0.05)。综合分析显示，较高的钙浓度与总体AMD风险降低相关。OR为0.89（95%CI=0.81，0.98）。
结论：这项研究提供了支持钙浓度与AMD及其亚型风险之间因果关系的证据，这可能对预防有重要影响，监测,和AMD的治疗。
目的：本研究旨在探讨25(OH)D浓度的因果关系。钙浓度，和膳食补充剂使用维生素D和钙对AMD及其亚型的风险。
方法：在已发表的欧洲血统全基因组关联研究（GWAS）中，将与25（OH）D和钙浓度相关的独立遗传变异用作工具变量。使用UKBiobank和FinnGen数据集的汇总数据进行双向双样本孟德尔随机化（MR）分析。进行敏感性分析以确保MR结果的稳健性。使用固定效应和随机效应模型进行荟萃分析，以提供全面可靠的估计。
结果：钙浓度的标准偏差增加与14%有关，17%,发生AMD的可能性降低13%(95%置信区间[CI]=0.77，0.97)，湿性AMD（95%CI=0.73，0.95），和干性AMD（95%CI=0.75，1.00），分别。基因预测的25(OH)D浓度与AMD及其亚型之间没有显著的因果关系(均P>0.05)。综合分析显示，较高的钙浓度与总体AMD风险降低相关。OR为0.89（95%CI=0.81，0.98）。
结论：这项研究提供了支持钙浓度与AMD及其亚型风险之间因果关系的证据，这可能对预防有重要影响，监测,和AMD的治疗。
