Mendelian randomization analysis suggests no causal effect of herpes zoster virus on stroke

Herpes zoster (HZ), also known as shingles, is a viral disease caused by the reactivation of varicella-zoster virus (VZV) in latently infected sensory ganglia. Since the 1970s, various reports have linked VZV-induced vasculopathy and stroke syndrome with HZ attacks. A retrospective cohort study, which is the largest of its kind, has confirmed that HZ is an independent risk factor for myocardial infarction and transient ischemic attack in UK adults over 18 years, up to 24 years after the acute episode. [ [1] Breuer J. Pacou M. Gautier A. Brown M.M. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology. 2014; 83: e27-e33 Crossref PubMed Scopus (43) Google Scholar ] Similar findings have also been reported in population cohort studies conducted in Taiwan [ [2] Kang J.H. Ho J.D. Chen Y.H. Lin H.C. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke. 2009; 40: 3443-3448 Crossref PubMed Scopus (180) Google Scholar ] and Denmark. [ [3] Sreenivasan N. Basit S. Wohlfahrt J. Pasternak B. Munch T.N. Nielsen L.P. Melbye M. The short- and long-term risk of stroke after herpes zoster - a nationwide population-based cohort study. PLoS One. 2013; 8e69156 Crossref Scopus (83) Google Scholar ] While prospective cohort designs may mitigate these limitations, residual confounding by unknown and unmeasured factors may still compromise the validity of the results. Mendelian Randomization (MR) employs genetic variants to infer causal relationships between traits and diseases, minimizing confounding typical in observational research. Therefore, the objective of our study was to analyze the causal effect HZ on stroke using MR analysis.