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175 226例患者,7 589 717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6 260例癫痫患者和176 107例健康对照者,16 380 349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's Q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.
Abstract
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 175 226 patients with 7 589 717 single nucleotide polymorphisms(SNPs).GWAS data for epilepsy were obtained from the Finn Gen database,which included 6 260 epilepsy cases and 176 107 healthy controls with 16 380 349 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's Q test 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 their β-values were in the same direction as the β-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's Q test 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.
维普
万方数据