虚弱与癫痫发生风险的因果关系:孟德尔随机化分析  

Causal Relationship between Frailty and Risk of Epilepsy:a Mendelian Randomization Analysis

作　　者：张帅帅 黄宇靖 贾肖扬 彭阳阳 李良宇 王桂华 杜爱玲[1] ZHANG Shuaishuai;HUANG Yujing;JIA Xiaoyang;PENG Yangyang;LI Liangyu;WANG Guihua;DU Aiing(Department of Neurological,the Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453000,China)

机构地区：[1]新乡医学院第二附属医院神经内科,河南省新乡市453000

出　　处：《实用心脑肺血管病杂志》2025年第1期67-70,共4页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：河南省医学科技攻关计划联合共建项目(豫卫科教函[2023]52号)。

摘　　要：目的采用孟德尔随机化(MR)分析方法探究虚弱与癫痫发生风险的因果关系。方法虚弱指数的全基因组关联分析(GWAS)汇总数据来源于Gwas Catalog数据库,包括175226例患者,7589717个单核苷酸多态性(SNP);癫痫的GWAS汇总数据来源于Finn Gen数据库,包括6260例癫痫患者和176107例健康对照者,16380349个SNP。本研究主要采用逆方差加权法(IVW)分析衰弱指数与癫痫发生风险的因果关系,采用MR-Egger回归、加权中位数法及加权模式法作为IVW的补充方法。采用Cochran'sQ检验、漏斗图分析SNP的统计学异质性,采用MR-Egger回归的截距项评估SNP的水平多效性,采用留一法分析单个SNP对MR分析结果的影响。结果IVW分析结果显示,衰弱指数与癫痫发生风险呈正相关[OR=1.584,95%CI(1.086~2.312)];MR-Egger回归、加权模式法分析结果显示,衰弱指数与癫痫发生风险之间无因果关系(P>0.05),但其β值与IVW的β值方向一致;加权中位数法分析结果显示,衰弱指数与癫痫发生风险呈正相关[OR=1.642,95%CI(1.036~2.603)]。Cochran'sQ检验、漏斗图分析结果显示,与衰弱指数强相关的SNP间无统计学异质性。MR-Egger回归的截距项分析结果显示,与衰弱指数强相关的SNP无水平多效性(P=0.987);留一法分析结果显示,逐一剔除单个SNP后,IVW分析结果无明显改变。结论虚弱与癫痫发生风险存在正向因果关系。Objective To explore the causal relationship between frailty and risk of epilepsy by mendelian randomization(MR)analysis.Methods Genome-wide association study(GWAS)data for frailty index were obtained from the Gwas Catalog database,which included 175226 patients with 7589717 single nucleotide polymorphisms(SNPs).GWAS data for epilepsy were obtained from the Finn Gen database,which included 6260 epilepsy cases and 176107 healthy controls with 16380349 SNPs.Inverse variance weighted(IVW)was used to explore the relationship between frailty and risk of epilepsy.MR-Egger regression,weighted median estimator,and weighted mode method analysis were used as complementary methods for IVW.Cochran'sQtest and funnel plot were used to analyze whether there was statistical heterogeneity between SNPs.The intercept term of MR-Egger regression was used to analyze the horizontal pleiotropy of SNPs.The leave-one-out method was used to analyze the impact of a single SNP on the MR analysis results.Results IVW analysis showed a positive relationship between frailty and risk of epilepsy[OR=1.584,95%CI(1.086-2.312)].MR-Egger regression and weighted mode method analysis showed that there was no causal relationship between frailty and risk of epilepsy(P>0.05),but theirβ-values were in the same direction as theβ-value of IVW;and weighted median method analysis showed that there was a positive relationship between frailty and risk of epilepsy[OR=1.642,95%CI(1.036-2.603)].Cochran'sQtest and funnel plot analysis showed that there was no statistical heterogeneity between SNPs strongly correlated with frailty index(P>0.05).The intercept term of MR-Egger regression method showed that there was no horizontal pleiotropy of SNPs strongly correlated with the frailty index(P=0.987).The leave-one-out method analysis showed that after excluding individual SNPs one by one,the results of IVW analysis showed that no significant change.Conclusion There is a positive causal relationship between frailty and risk of epilepsy.

关 键 词：癫痫 虚弱 因果关系 孟德尔随机化分析 

分 类 号：R742.1[医药卫生—神经病学与精神病学]