■人类疱疹病毒（HHV）感染与肌萎缩侧索硬化症（ALS）之间的因果关系一直存在争议。这项研究调查了单纯疱疹病毒（HSV）之间的因果关系，水痘-带状疱疹病毒（VZV），EB病毒(EBV)巨细胞病毒（CMV），通过双向孟德尔随机化（MR）方法，HHV-6和HHV-7感染和ALS。
■全基因组关联研究（GWAS）数据库采用逆方差加权（IVW）分析，MR-Egger,加权中位数，简单模式，和加权模式方法。MR-Egger截距测试,MR-PRESSO试验,Cochran的Q测试,漏斗图,和leaveone-out分析用于验证MR结果的有效性和鲁棒性。
■在IVW的正向MR分析中，遗传预测的HSV感染[优势比（OR）=0.9917;95％置信区间（CI）：0.9685-1.0154;p=0.4886]，HSV角膜炎和角膜结膜炎（OR=0.9897;95％CI：0.9739-1.0059;p=0.2107），肛门生殖器HSV感染(OR=1.0062;95%CI:0.9826-1.0304;p=0.6081),VZVIgG（OR=1.0003；95%CI：0.9849-1.0160；p=0.9659），EBVIgG（OR=0.9509；95%CI：0.8879-1.0183；p=0.1497），CMV（OR=0.9481；95%CI：0.8680-1.0357；p=0.2374），HHV-6IgG(OR=0.9884;95%CI:0.9486-1.0298;p=0.5765)和HHV-7IgG(OR=0.9991;95%CI:0.9693-1.0299;p=0.9557)与ALS无因果关系。IVW的反向MR分析显示了可比的结果，表明HHVs感染和ALS之间没有联系。通过敏感性分析验证了研究结果的信度和效度。
■根据MR研究，没有证据表明遗传预测的HHV(HSV，VZV,EBV,CMV,HHV-6和HHV-7）和ALS。
UNASSIGNED: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.
UNASSIGNED: The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran\'s Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.
UNASSIGNED: In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis.
UNASSIGNED: According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.
PDF(Pubmed)