基于孟德尔随机化的缺血性脑卒中与癫痫的因果关系研究

Causality between ischemic stroke and epilepsy based on Mendelian randomization

目的探索缺血性脑卒中与不同类型癫痫之间的因果关系,为缺血性脑卒中与癫痫的发病风险提供遗传学证据支持。方法基于全基因组关联分析的汇总数据,采用MR-Egger回归、加权中位数法、逆方差加权法进行孟德尔随机化(Mendelian randomization,MR)分析,使用MR-Egger回归检验、MR-PRESSO检验和留一法进行敏感性分析。结果两样本MR分析表明缺血性脑卒中与癫痫(OR=1.10,P=0.036)和全面性癫痫(OR=1.25,P=0.001)的风险表现出因果关系,但与局灶性癫痫(OR=1.06,P=0.360)之间未显现因果关系。另外,舒张压(OR=1.12,P=0.002)和BMI(OR=1.08,P=0.015)也与癫痫呈现因果关系,进一步使用多变量MR分析方法,校正混杂因素影响之后,只有缺血性脑卒中(OR=1.18,P=3.770×10^(-6))和癫痫风险之间呈现因果关系。结论缺血性脑卒中和全面性癫痫风险之间存在因果关联,可据此进行卒中后癫痫的风险分层。

ObjectiveTo explore the causal relationship between ischemic stroke and different types of epilepsy so as to provide genetic evidence for the risk of epilepsy after ischemic stroke.MethodsBased on the summary data of genome-wide association study,Mendelian randomization(MR)analysis was performed with MR-Egger regression,weighted median and inverse-variance weighting.Sensitivity analysis was conducted by using MR-Egger regression test,MR-PRESSO test and leave-one-out method.ResultsTwo-sample MR analysis showed that there was a causal relationship between ischemic stroke and the risk of epilepsy(OR=1.10,P=0.036)and generalized epilepsy(OR=1.25,P=0.001),but no such relationship was observed with the risk of focal epilepsy(OR=1.06,P=0.360).In addition,diastolic blood pressure(OR=1.12,P=0.002)and BMI(OR=1.08,P=0.015)also had a causal relationship with the risk of epilepsy.After adjusting confounding factors,multivariate MR analysis revealed that only ischemic stroke(OR=1.18,P=3.770×10^(-6))and epilepsy risk had a causal relationship.ConclusionThere is a causal relationship between ischemic stroke and the risk of generalized epilepsy,which can be used to stratify the risk of post-stroke epilepsy.