AUTHOR=Zheng Qingcong , Wang Du , Lin Rongjie , Chen Yuchao , Huang Haoen , Xu Zixing , Zheng Chunfu , Xu Weihong 

TITLE=Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1299122

DOI=10.3389/fnins.2023.1299122

ISSN=1662-453X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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; <italic>p</italic> = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739–1.0059; <italic>p</italic> = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826–1.0304; <italic>p</italic> = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849–1.0160; <italic>p</italic> = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879–1.0183; <italic>p</italic> = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680–1.0357; <italic>p</italic> = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486–1.0298; <italic>p</italic> = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693–1.0299; <italic>p</italic> = 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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>