Chen Sirui, Zhang Ningning, Zhang Ruirui, Zhang Lan, Luo Dadong, Li Junqiang, Liu Yaqing, Wang Yunan, Duan Xinyue, Tian Xin, Wang Tiancheng
The Second Hospital & Clinical Medical School Lanzhou University Lanzhou China.
Department of Neurology, Epilepsy Center, The Second Hospital & Clinical Medical School Lanzhou University Lanzhou China.
Ibrain. 2025 Jan 7;11(1):98-105. doi: 10.1002/ibra.12191. eCollection 2025 Spring.
This study aimed to investigate the causal relationship between systemic lupus erythematosus (SLE) and juvenile myoclonic epilepsy (JME). Univariable and reverse Mendelian randomization (MR) analyses were performed to investigate the potential causal associations between SLE, systemic autoimmune disorders (SADs), and JME. Two-step mediation MR analysis was further performed to explore indirect factors that may influence the relationship between SLE and JME. Summary data on SADs were extracted from the Integrative Epidemiology Unit Open genome-wide association study database, and summary statistics for JME were acquired from the International League Against Epilepsy Consortium. The inverse-variance weighted (IVW) method was used for primary analysis, supplemented by MR-Egger and weighted median. In the univariable MR analysis, IVW results indicated a causal relationship between SLE and an increased risk of JME (odds ratio = 1.0030, 95% confidence interval, 1.0004-1.0057; = 0.023). The subsequent mediation MR analysis showed that inflammatory cytokines may not be the mediating factors between SLE and JME, while the inverse MR analysis found no significant relationship. Our study indicated that genetic susceptibility to SLE was causally linked to JME. However, subsequent mediation analysis failed to identify the potential mediators that could influence this relationship. Moreover, evidence suggested that other SADs were not causally associated with JME. This study may provide guidance for screening risk factors for seizures and exploring potential treatments in SLE and JME, and even all SADs and JME.
本研究旨在调查系统性红斑狼疮（SLE）与青少年肌阵挛性癫痫（JME）之间的因果关系。进行了单变量和反向孟德尔随机化（MR）分析，以研究SLE、系统性自身免疫性疾病（SADs）和JME之间的潜在因果关联。进一步进行了两步中介MR分析，以探索可能影响SLE与JME关系的间接因素。从综合流行病学单位开放全基因组关联研究数据库中提取了SADs的汇总数据，并从国际抗癫痫联盟协会获得了JME的汇总统计数据。主要分析采用逆方差加权（IVW）方法，并辅以MR-Egger和加权中位数法。在单变量MR分析中，IVW结果表明SLE与JME风险增加之间存在因果关系（优势比=1.0030，95%置信区间为0.0004-1.0057；P=0.023）。随后的中介MR分析表明，炎性细胞因子可能不是SLE与JME之间的中介因素，而反向MR分析未发现显著关系。我们的研究表明，SLE的遗传易感性与JME存在因果联系。然而，随后的中介分析未能确定可能影响这种关系的潜在中介因素。此外，有证据表明其他SADs与JME无因果关联。本研究可为筛查癫痫发作的危险因素以及探索SLE和JME甚至所有SADs和JME的潜在治疗方法提供指导。
