Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China.
Hainan Provincial Bureau of Disease Prevention and Control, Haikou, 570100, China.
Sci Rep. 2024 Aug 24;14(1):19670. doi: 10.1038/s41598-024-70758-z.
Observational studies have suggested the potential benefits of several medications for Parkinson's disease (PD) and their potential for repurposing. However, the conclusions drawn from these studies are not entirely consistent. To address this inconsistency, we used the two-sample Mendelian randomization (MR) method to explore the putative causal relationships between 23 medications and the risk and progression of PD. We applied inverse-variance weighted meta-analysis (IVW) to combine MR estimates. Additionally, sensitivity analyses were conducted to evaluate the robustness of the results. Our genetic evidence suggests that thyroid preparations and calcium channel blockers reduce the risk of PD, and salicylic acid and derivatives slow the progression of PD motor symptoms. Additionally, genetic evidence also suggests that four medications were associated with PD risk or progression, but the sensitivity analysis revealed that three of the medications may have interference caused by reverse causality. Our findings suggest that there are weak causal relationships between several medications and the risk or progression of PD. Though further replication studies are needed to verify these findings, these new insights may help in understanding the etiology of the disease, generate new clues related to drug discovery, and quantify the risk of future drug intake.
观察性研究表明,几种治疗帕金森病 (PD) 的药物具有潜在益处,并可能具有重新定位的潜力。然而,这些研究得出的结论并不完全一致。为了解决这种不一致性,我们使用两样本孟德尔随机化 (MR) 方法来探讨 23 种药物与 PD 风险和进展之间的潜在因果关系。我们应用逆方差加权荟萃分析 (IVW) 来合并 MR 估计值。此外,还进行了敏感性分析以评估结果的稳健性。我们的遗传证据表明,甲状腺制剂和钙通道阻滞剂可降低 PD 的风险,而水杨酸及其衍生物可减缓 PD 运动症状的进展。此外,遗传证据还表明,有四种药物与 PD 风险或进展相关,但敏感性分析表明,其中三种药物可能存在由反向因果关系引起的干扰。我们的研究结果表明,几种药物与 PD 的风险或进展之间存在较弱的因果关系。尽管需要进一步的复制研究来验证这些发现,但这些新的见解可能有助于了解疾病的病因,为药物发现提供新的线索,并量化未来药物摄入的风险。