Tian Ruoshi, Yu Wenlong, Hu Jiaqing, Yang Yan, He Xirui
School of Bioengineering, Zunyi Medical University, Zhuhai, China.
School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, China.
Epilepsia Open. 2025 Oct;10(5):1415-1425. doi: 10.1002/epi4.70102. Epub 2025 Aug 17.
Epidemiological data indicates that individuals with epilepsy exhibit an elevated susceptibility to autoimmune disorders, and conversely, those with systemic autoimmune diseases (SAD) demonstrate a heightened predisposition to epilepsy. Although an increasing number of publications support this association, the causal direction remains undetermined. This investigation offers evidence supporting a causal relationship between these conditions through a bidirectional two-sample Mendelian randomization (MR) analysis.
Bidirectional two-sample MR analyses were performed to investigate the causal relationships and directionality between various epilepsy subtypes and eight SAD. The analysis utilized genome-wide association study (GWAS) summary data for the following conditions: type 1 diabetes, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis, coeliac disease, multiple sclerosis (MS), ulcerative colitis, and Crohn's disease.
In this study, causal analyses were performed for different epilepsy subtypes and SAD disorders. In the Inverse-Variance Weighted (IVW) model, the MR study indicated that focal epilepsy increased the risk of IBD [odds ratio (OR): 1.15, confidence interval (CI): 1.02-1.30, p: 0.027] and MS [OR: 1.25, CI: 1.07-1.47, p: 0.004]. Childhood absence epilepsy increased the risk of MS [OR: 0.25, CI: 0.07-0.90, p: 0.034]. Reverse analyses showed that SLE increased the risk of myoclonic epilepsy in adolescents [OR: 1.01, CI: 1.00-1.01, p: 0.042], and IBD [OR: 0.99, CI: 0.99-1.00, p: 0.013], and celiac disease [OR: 0.99, CI: 0.99-1.00, p: 0.021] reduced the risk of generalized epilepsy. The results demonstrated homogeneity, and the MR-Egger directions were concordant.
This study shows that epilepsy is a causal risk factor for both IBD and MS, providing new insights into the prevention of SAD in people with epilepsy.
This paper employs a bidirectional two-sample MR analysis to investigate the genetic correlation between epilepsy and autoimmune diseases, revealing potential associations between the onset of epilepsy and MS as well as IBD. Further exploration in this area requires support from clinical data.
流行病学数据表明，癫痫患者患自身免疫性疾病的易感性升高，反之，患有系统性自身免疫性疾病（SAD）的个体患癫痫的倾向也更高。尽管越来越多的出版物支持这种关联，但因果方向仍未确定。本研究通过双向双样本孟德尔随机化（MR）分析提供了支持这些疾病之间因果关系的证据。
进行双向双样本MR分析，以研究各种癫痫亚型与八种SAD之间的因果关系和方向性。分析利用了以下疾病的全基因组关联研究（GWAS）汇总数据：1型糖尿病、系统性红斑狼疮（SLE）、炎症性肠病（IBD）、类风湿性关节炎、乳糜泻、多发性硬化症（MS）、溃疡性结肠炎和克罗恩病。
在本研究中，对不同的癫痫亚型和SAD疾病进行了因果分析。在逆方差加权（IVW）模型中，MR研究表明，局灶性癫痫增加了患IBD的风险[比值比（OR）：1.15，置信区间（CI）：1.02-1.30，p：0.027]和MS的风险[OR：1.25，CI：1.07-1.47，p：0.004]。儿童失神癫痫增加了患MS的风险[OR：0.25，CI：0.07-0.90，p：0.034]。反向分析表明，SLE增加了青少年肌阵挛癫痫的风险[OR：1.01，CI：1.00-1.01，p：0.042]，IBD[OR：0.99，CI：0.99-1.00，p：0.013]和乳糜泻[OR：0.99，CI：0.99-1.00，p：0.021]降低了全身性癫痫的风险。结果显示出同质性，且MR-Egger方向一致。
本研究表明，癫痫是IBD和MS的因果危险因素，为预防癫痫患者的SAD提供了新的见解。
本文采用双向双样本MR分析来研究癫痫与自身免疫性疾病之间的遗传相关性，揭示了癫痫发作与MS以及IBD之间的潜在关联。该领域的进一步探索需要临床数据的支持。
