Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China.
The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
Medicine (Baltimore). 2024 Sep 13;103(37):e39400. doi: 10.1097/MD.0000000000039400.
Using genome-wide association study data from European populations, this research clarifies the causal relationship between plasma metabolites and age-related macular degeneration (AMD) and employs Metabo Analyst 5.0 for enrichment analysis to investigate their metabolic pathways. Employing Mendelian randomization analysis, this study leveraged single nucleotide polymorphisms significantly associated with plasma metabolites as instrumental variables. This approach established a causal link between metabolites and AMD. Analytical methods such as inverse-variance weighted, Mendelian randomization-Egger, and weighted median were applied to validate causality. Mendelian Randomization Pleiotropy Residual Sum and Outlier was utilized for outlier detection and correction, and Cochran's Q test was conducted to assess heterogeneity. To delve deeper into the metabolic characteristics of AMD, metabolic enrichment analysis was performed using Metabo Analyst 5.0. These combined methods provided a robust framework for elucidating the metabolic underpinnings of AMD. The 2-sample MR analysis, after meticulous screening, identified causal relationships between 88 metabolites and AMD. Of these, 16 metabolites showed a significant causal association. Following false discovery rate correction, 3 metabolites remained significantly associated, with androstenediol (3 beta, 17 beta) disulfate (2) exhibiting the most potent protective effect against AMD. Further exploration using Metabo Analyst 5.0 highlighted 4 metabolic pathways potentially implicated in AMD pathogenesis. This pioneering MR study has unraveled the causal connections between plasma metabolites and AMD. It identified several metabolites with a causal impact on AMD, with 3 maintaining significance after FDR correction. These insights offer robust causal evidence for future clinical applications and underscore the potential of these metabolites as clinical biomarkers in AMD screening, treatment, and prevention strategies.
利用来自欧洲人群的全基因组关联研究数据，本研究阐明了血浆代谢物与年龄相关性黄斑变性（AMD）之间的因果关系，并采用 Metabo Analyst 5.0 进行富集分析以研究其代谢途径。本研究利用与血浆代谢物显著相关的单核苷酸多态性作为工具变量，采用孟德尔随机化分析方法。该方法在代谢物和 AMD 之间建立了因果关系。采用逆方差加权、孟德尔随机化-Egger 和加权中位数等分析方法来验证因果关系。孟德尔随机化偏倚剩余和异常值用于异常值检测和校正，并用 Cochran's Q 检验评估异质性。为了深入研究 AMD 的代谢特征，采用 Metabo Analyst 5.0 进行代谢富集分析。这些综合方法为阐明 AMD 的代谢基础提供了一个稳健的框架。经过仔细筛选的 2-sample MR 分析确定了 88 种代谢物与 AMD 之间的因果关系。其中，16 种代谢物表现出显著的因果关联。经过错误发现率校正后，有 3 种代谢物仍然存在显著关联，其中雄烯二酮（3β，17β）二硫酸盐（2）对 AMD 具有最强的保护作用。进一步使用 Metabo Analyst 5.0 进行探索，突出了 4 个可能与 AMD 发病机制相关的代谢途径。这项开创性的 MR 研究揭示了血浆代谢物与 AMD 之间的因果关系。它确定了几种对 AMD 具有因果影响的代谢物，其中 3 种在 FDR 校正后仍具有显著性。这些见解为未来的临床应用提供了强有力的因果证据，并强调了这些代谢物作为 AMD 筛查、治疗和预防策略中的临床生物标志物的潜力。
