使用孟德尔随机化方法对药物使用与神经退行性疾病风险之间的关联进行系统筛查。

Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.

作者信息

Wang Wenjing, Zhang Linjing, Cao Wen, Xia Kailin, Huo Junyan, Huang Tao, Fan Dongsheng

机构信息

Department of Neurology, Peking University Third Hospital, Beijing 100191, China.

Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing 100191, China.

出版信息

Biomedicines. 2023 Jul 7;11(7):1930. doi: 10.3390/biomedicines11071930.

DOI:10.3390/biomedicines11071930

PMID:37509570

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10377701/

Abstract

BACKGROUND

Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

METHODS

A two-sample mendelian randomization (MR) approach was conducted. Estimates were calculated using the inverse-variance weighted (IVW) method as the main model. A sensitivity analysis and a pleiotropy analysis were performed to identify potential violations.

RESULTS

Genetically predisposition to antihypertensives (OR = 0.809, 95% CI = 0.668-0.981, = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909-0.988, = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789-0.979, = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884-0.988, = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699-0.973, = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756-0.983, = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042-1.461, = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025-1.148, = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078-1.553, = 0.006) were associated with an increased risk of ALS.

CONCLUSIONS

We presented a systematic view concerning the causal associations between medications and NDs, which will promote the etiology discovery, drug repositioning and patient management for NDs.

摘要

背景

系统评估药物与神经退行性疾病之间的因果关联对于确定疾病病因和新疗法具有重要意义。在此，我们研究了23种现有药物类别与主要神经退行性疾病（NDs）之间的假定因果关联，包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS）。

方法

采用两样本孟德尔随机化（MR）方法。使用逆方差加权（IVW）方法作为主要模型计算估计值。进行敏感性分析和多效性分析以识别潜在的违规情况。

结果

遗传易感性导致使用抗高血压药（OR = 0.809，95%CI = 0.668 - 0.981，P = 0.031）、甲状腺制剂（OR = 0.948，95%CI = 0.909 - 0.988，P = 0.011）和免疫抑制剂（OR = 0.879，95%CI = 0.789 - 0.979，P = 0.018）与AD风险降低相关。甲状腺制剂（OR = 0.934，95%CI = 0.884 - 0.988，P = 0.017）、免疫抑制剂（OR = 0.825，95%CI = 0.699 - 0.973，P = 0.022）和糖皮质激素（OR = 0.862，95%CI = 0.756 - 0.983，P = 0.027）的遗传代理与PD风险降低存在因果关联。遗传决定的抗血栓药物（OR = 1.234，95%CI = 1.042 - 1.461，P = 0.015）、HMG CoA还原酶抑制剂（OR = 1.085，95%CI = 1.025 - 1.148，P = 0.005）以及水杨酸及其衍生物（OR = 1.294，95%CI = 1.078 - 1.553，P = 0.006）与ALS风险增加相关。