Department of Neurology, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China.
School of Mental Health, Guangzhou Medical University, Guangzhou, China.
Brain Behav. 2024 Oct;14(10):e70018. doi: 10.1002/brb3.70018.
Epilepsy and amyotrophic lateral sclerosis (ALS) are common neurological disorders. The association between the two disorders has been raised in observational studies. However, it is uncertain to what extent they have mutual causal effects. In this study, we aimed to investigate their causal association using a two-sample Mendelian randomization (MR) method.
We performed a two-sample bidirectional MR analysis to evaluate the causal association of epilepsy with the risk of ALS. Publicly published genome-wide association study statistics for epilepsy and ALS were used in the study. The primary analysis included genetic variants with a p value of less than 1 × 10 as instrumental variables. We applied several alternative methods, including inverse variance weighting, weighted median, simple mode, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier, and statistical graphs to assess the associations of epilepsy and its subtype with the risk of ALS. Reverse MR analyses were also performed to examine the association of ALS with the risk of epilepsy.
The primary MR analysis found no causal effect of epilepsy on risk of ALS (odds ration [OR]: 1.133, 95% confidence interval [CI]: 0.964-1.332, p = .130). Among subtypes of epilepsy, it also failed to observe any causal association between general epilepsy and ALS (OR: 1.036, 95% CI: 0.969-1.108, P = .300). However, focal epilepsy contributed to an increase in the risk of ALS (OR: 1.177, 95% CI: 1.027-1.348, p = .019). Moreover, the investigation of reverse causalities did not reveal significant results.
The current study supports a causal influence of focal epilepsy on ALS risk. Future studies are needed to explore its potential role in ALS.
癫痫和肌萎缩侧索硬化症（ALS）是常见的神经疾病。在观察性研究中提出了这两种疾病之间的关联。然而，它们在多大程度上具有相互因果效应尚不确定。在这项研究中，我们旨在使用两样本孟德尔随机化（MR）方法来研究它们之间的因果关系。
我们进行了两样本双向 MR 分析，以评估癫痫与 ALS 风险之间的因果关系。该研究使用了公开发表的癫痫和 ALS 全基因组关联研究统计数据。主要分析包括作为工具变量的 p 值小于 1×10 的遗传变异。我们应用了几种替代方法，包括逆方差加权、加权中位数、简单模式、加权模式、MR-Egger 回归和 MR 多效性残差和异常值以及统计图形，以评估癫痫及其亚型与 ALS 风险的关联。还进行了反向 MR 分析，以检查 ALS 与癫痫风险的关联。
主要的 MR 分析发现癫痫对 ALS 风险没有因果影响（比值比 [OR]：1.133，95%置信区间 [CI]：0.964-1.332，p=0.130）。在癫痫的亚型中，也未观察到一般癫痫与 ALS 之间存在任何因果关系（OR：1.036，95%CI：0.969-1.108，P=0.300）。然而，局灶性癫痫会增加 ALS 的风险（OR：1.177，95%CI：1.027-1.348，p=0.019）。此外，对反向因果关系的调查没有发现显著结果。
目前的研究支持局灶性癫痫对 ALS 风险的因果影响。需要进一步的研究来探索其在 ALS 中的潜在作用。
