Lei Chaofang, Chen Jiaxu, Chen Zhigang, Xiao Yonghong, Chen Jianbei, Ma Chongyang, Yang Miaomiao, Wu Dahua, Xie Le
Department of Neurology, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Medicine (Baltimore). 2025 Jun 20;104(25):e42847. doi: 10.1097/MD.0000000000042847.
In this study, we used the Mendelian randomization (MR) method to systematically examine whether there is a bidirectional causal relationship between amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). We analyzed data from 6,44,924 participants using MR to evaluate causality. We employed inverse variance weighted and MR-Egger regression tests for MR analysis. Additionally, we performed sensitivity analyses using the MR-Egger test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. The inverse variance weighted analysis found no evidence of a risk effect between ALS and the neurodegenerative diseases AD, PD, FTD, MSA, and DLB. However, the MR-Egger analysis showed that both AD (odds ratio: 1.079, 95% confidence interval: 1.017-1.145, P = .029) and PD (odds ratio: 1.210, 95% confidence interval: 1.046-1.401, P = .020) have a risk effect on ALS, indicating that AD and PD increase the risk of ALS. Our MR analysis suggests that AD and PD may have a potential causal relationship with ALS. Conversely, ALS does not appear to have a causal relationship with the other neurodegenerative diseases examined (FTD, MSA, DLB).
在本研究中，我们使用孟德尔随机化（MR）方法系统地研究肌萎缩侧索硬化症（ALS）与阿尔茨海默病（AD）、帕金森病（PD）、额颞叶痴呆（FTD）、多系统萎缩（MSA）和路易体痴呆（DLB）之间是否存在双向因果关系。我们使用MR分析了644924名参与者的数据以评估因果关系。我们采用逆方差加权法和MR-Egger回归检验进行MR分析。此外，我们使用MR-Egger检验和孟德尔随机化多效性残差和离群值进行了敏感性分析。逆方差加权分析未发现ALS与神经退行性疾病AD、PD、FTD、MSA和DLB之间存在风险效应的证据。然而，MR-Egger分析表明，AD（比值比：1.079，95%置信区间：1.017-1.145，P = 0.029）和PD（比值比：1.210，95%置信区间：1.046-1.401，P = 0.020）对ALS有风险效应，表明AD和PD会增加ALS的风险。我们的MR分析表明，AD和PD可能与ALS存在潜在因果关系。相反，ALS似乎与所研究的其他神经退行性疾病（FTD、MSA、DLB）没有因果关系。
