Abstract：
BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy.
METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy.
RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 ∼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 ∼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy.
CONCLUSIONS: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.
METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy.
RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 ∼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 ∼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy.
CONCLUSIONS: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.
摘要：
背景：神经炎症在癫痫中起着重要的病理生理作用；然而，免疫细胞与癫痫之间的确切联系尚不清楚.本研究采用孟德尔随机化(MR)分析731种免疫细胞性状与癫痫的因果关系。
方法：基于全基因组关联研究（GWAS）的数据，我们进行了双向双样本MR分析,以研究免疫细胞表型对癫痫的潜在影响.使用五种MR方法对结果进行分析，以逆方差加权(IVW)方法为主要方法，并使用错误发现率(FDR)方法对结果进行校正。进行敏感性分析以测试异质性和水平多效性。
结果：修正FDR后，4种免疫特征与癫痫发病风险显著相关:记忆中CD25的表达(OR=1.04,95%CI=1.02~1.06,P=2.55×10-4),IgD+CD38dim(OR=1.05,95%CI=1.02~1.08,P=4.73×10-4),CD24+CD27+(OR=1.04,95%CI=1.02~1.06,P=4.82×10-4),和IgD-CD38dim（OR=1.04，95%CI=1.02~1.06，P=1.04×10-3）B细胞。全身性癫痫的风险与两种免疫细胞特征显着相关，而局灶性癫痫与7种免疫细胞特征显著相关。此外，免疫细胞表型不受遗传预测的癫痫的影响。
结论：这项MR研究肯定了循环免疫细胞与癫痫之间的因果关系。为进一步了解癫痫的免疫机制和发现新的治疗靶点提供指导。
方法：基于全基因组关联研究（GWAS）的数据，我们进行了双向双样本MR分析,以研究免疫细胞表型对癫痫的潜在影响.使用五种MR方法对结果进行分析，以逆方差加权(IVW)方法为主要方法，并使用错误发现率(FDR)方法对结果进行校正。进行敏感性分析以测试异质性和水平多效性。
结果：修正FDR后，4种免疫特征与癫痫发病风险显著相关:记忆中CD25的表达(OR=1.04,95%CI=1.02~1.06,P=2.55×10-4),IgD+CD38dim(OR=1.05,95%CI=1.02~1.08,P=4.73×10-4),CD24+CD27+(OR=1.04,95%CI=1.02~1.06,P=4.82×10-4),和IgD-CD38dim（OR=1.04，95%CI=1.02~1.06，P=1.04×10-3）B细胞。全身性癫痫的风险与两种免疫细胞特征显着相关，而局灶性癫痫与7种免疫细胞特征显著相关。此外，免疫细胞表型不受遗传预测的癫痫的影响。
结论：这项MR研究肯定了循环免疫细胞与癫痫之间的因果关系。为进一步了解癫痫的免疫机制和发现新的治疗靶点提供指导。
