Hu Yang, Lin Duo, Wu Dongmei, Zhang Yuqing, Li Gongbo
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, Zhongshan Hospital of Traditional Chinese Medicine, Guangdong, China.
Epilepsia Open. 2024 Dec;9(6):2274-2282. doi: 10.1002/epi4.13058. Epub 2024 Sep 28.
Numerous observational studies have found a relationship between systemic lupus erythematosus (SLE) and epilepsy; however, their causal relationship remains unclear. This study aimed to investigate the causal role of SLE in epilepsy or any of its subtypes using a two-sample Mendelian randomization (MR) analysis.
Single nucleotide polymorphisms (SNPs) linked to SLE were utilized as instrumental variables in MR analysis to assess their causal impact on epilepsy. The primary MR findings were derived using the inverse variance weighted (IVW) method, which was further supported by the weighted median and MR-Egger regression techniques. Additionally, sensitivity analyses, including Cochran's Q test and pleiotropy tests, were conducted to evaluate the influence of these SNPs on epilepsy, particularly looking for signs of horizontal pleiotropy and heterogeneity.
We selected 43 SNPs that reached genome-wide significance from genome-wide association studies (GWASs) on SLE to serve as instrumental variables in this study. The IVW method showed no evidence to support a causal association between SLE and epilepsy (all epilepsy: odds ratio (OR) = 1.006, 95% confidence interval (CI) = 0.994-1.018; focal epilepsy: OR = 1.006, 95% CI = 0.994-1.019; generalized epilepsy: OR = 1.015, 95% CI = 0.996-1.035). Other MR complementary methods revealed consistent results. Furthermore, there was no evidence indicating heterogeneity or horizontal pleiotropy.
The findings of MR analysis did not support a genetically predicted causal relationship between SLE and epilepsy, but emphasized the need for further research on shared pathophysiological mechanisms, particularly the role of immune system abnormalities and potential influences such as chronic inflammation and therapeutic interventions.
The etiology of epilepsy is complex and diverse, including immune factors. Through a Mendelian randomization analysis, we did not find evidence of a genetic causal relationship between systemic lupus erythematosus and epilepsy. However, this does not invalidate epidemiological evidence, and further exploration is needed to investigate factors influencing the relationship between the two.
众多观察性研究发现系统性红斑狼疮（SLE）与癫痫之间存在关联；然而，它们之间的因果关系仍不明确。本研究旨在通过两样本孟德尔随机化（MR）分析来探究SLE在癫痫或其任何亚型中的因果作用。
与SLE相关的单核苷酸多态性（SNP）被用作MR分析中的工具变量，以评估它们对癫痫的因果影响。主要的MR结果采用逆方差加权（IVW）方法得出，加权中位数和MR-Egger回归技术进一步支持了该结果。此外，还进行了敏感性分析，包括Cochran's Q检验和多效性检验，以评估这些SNP对癫痫的影响，尤其关注水平多效性和异质性的迹象。
我们从SLE的全基因组关联研究（GWAS）中选择了43个达到全基因组显著性的SNP作为本研究的工具变量。IVW方法没有证据支持SLE与癫痫之间存在因果关联（所有癫痫：比值比（OR）=1.006，95%置信区间（CI）=0.994-1.018；局灶性癫痫：OR=1.006，95%CI=0.994-1.019；全身性癫痫：OR=1.015，95%CI=0.996-1.035）。其他MR补充方法也得出了一致的结果。此外，没有证据表明存在异质性或水平多效性。
MR分析的结果不支持SLE与癫痫之间存在遗传预测的因果关系，但强调需要进一步研究共同的病理生理机制，特别是免疫系统异常的作用以及慢性炎症和治疗干预等潜在影响。
癫痫的病因复杂多样，包括免疫因素。通过孟德尔随机化分析，我们没有发现系统性红斑狼疮与癫痫之间存在遗传因果关系的证据。然而，这并不否定流行病学证据，需要进一步探索以研究影响两者关系的因素。
