Zhang Wan, Wu Pengfei, Yin Rui, Sun Meichen, Zhang Rongsen, Liao Xiaoyao, Lin Yuhong, Lu Hui
Department of Biology, Boston University, Boston, MA, United States.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States.
Front Neurosci. 2022 Mar 1;16:817067. doi: 10.3389/fnins.2022.817067. eCollection 2022.
Previous studies have suggested an association between infection with herpes simplex virus (HSV) and liability to multiple sclerosis (MS), but it remains largely unknown whether the effect is causal. We performed a two-sample Mendelian randomization (MR) study to explore the relationship between genetically predicted HSV infection and MS risk. Genetic instrumental variables for diagnosed infections with HSV ( < 5 × 10) were retrieved from the FinnGen study, and single nucleotide polymorphisms associated with circulating immunoglobulin G (IgG) levels of HSV-1 and HSV-2 and corresponding summary-level statistics of MS were obtained from genome-wide association studies of the European-ancestry. Inverse-variance weighted MR was employed as the primary method and multiple sensitivity analyses were performed. Genetically proxied infection with HSV was not associated with the risk of MS (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90-1.02; = 0.22) per one-unit increase in log-OR of herpes viral infections. MR results provided no evidence for the relationship between circulating HSV-1 IgG levels and MS risks (OR = 0.91; 95% CI, 0.81-1.03; = 0.37), and suggested no causal effect of HSV-2 IgG (OR = 1.04; 95% CI, 0.96-1.13; = 0.32). Additional sensitivity analyses confirmed the robustness of these null findings. The MR study did not support the causal relationship between genetic susceptibly to HSV and MS in the European population. Further studies are still warranted to provide informative knowledge, and triangulating evidence across multiple lines of evidence are necessary to plan interventions for the treatment and prevention of MS.
先前的研究表明，单纯疱疹病毒（HSV）感染与多发性硬化症（MS）易感性之间存在关联，但这种影响是否具有因果关系在很大程度上仍不清楚。我们进行了一项两样本孟德尔随机化（MR）研究，以探讨基因预测的HSV感染与MS风险之间的关系。从芬兰基因研究中检索出诊断为HSV感染（<5×10）的基因工具变量，并从欧洲血统的全基因组关联研究中获得与HSV-1和HSV-2循环免疫球蛋白G（IgG）水平相关的单核苷酸多态性以及MS的相应汇总统计数据。采用逆方差加权MR作为主要方法，并进行了多项敏感性分析。每增加一个单位的疱疹病毒感染对数优势比，基因代理的HSV感染与MS风险无关（优势比[OR]，0.96；95%置信区间[CI]，0.90-1.02；P=0.22）。MR结果没有提供循环HSV-1 IgG水平与MS风险之间关系的证据（OR=0.91；95%CI，0.81-1.03；P=0.37），并表明HSV-2 IgG没有因果效应（OR=1.04；95%CI，0.96-1.13；P=0.32）。额外的敏感性分析证实了这些阴性结果的稳健性。MR研究不支持欧洲人群中HSV遗传易感性与MS之间的因果关系。仍有必要进行进一步研究以提供有用的知识，并且需要跨多条证据进行三角验证，以便为MS的治疗和预防制定干预措施。
