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基于单核苷酸多态性的神经退行性疾病与癫痫风险增加的关联:一项孟德尔随机化研究。

Association Between Neurodegenerative Diseases and an Increased Risk of Epilepsy Based on Single Nucleotide Polymorphisms: A Mendelian Randomization Study.

机构信息

Department of Neurosurgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.

出版信息

Mol Neurobiol. 2024 Aug;61(8):5950-5957. doi: 10.1007/s12035-024-03955-6. Epub 2024 Jan 23.

Abstract

Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.

摘要

癫痫是一种常见的神经系统疾病,其特征是短暂的脑功能障碍,归因于多种因素。本研究旨在探讨神经退行性疾病,特别是阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)和多发性硬化症(MS),是否对癫痫有因果影响。基于全基因组关联研究中的单核苷酸多态性,采用孟德尔随机化(MR)方法分析神经退行性疾病(AD、PD、ALS 和 MS)与癫痫之间的因果关系,包括逆方差加权、加权中位数、MR-Egger 和加权模式方法。MR-Egger 截距、MR-PRESSO 和异质性检验评估了 MR 分析结果的可靠性和稳定性。对 MS 和癫痫进行了 43 个 SNP 的 MR 分析。逆方差加权法显示 MS 与癫痫风险增加之间存在显著的因果关系(优势比 1.046;95%置信区间 1.001-1.093;P = 0.043)。然而,AD(P = 0.986)、PD(P = 0.894)和 ALS(P = 0.533)与癫痫之间没有因果关系。敏感性分析表明结果稳健。MR 研究证实了遗传预测 MS 与癫痫之间的因果关系,但不支持遗传预测 AD、PD 和 ALS 与癫痫之间的因果关系。

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