Association of Ischemic Stroke with Zoster Risk: A Mendelian Randomized Study.

Abstract

Recent observational investigations suggest a likely correlation between stroke lacking a blood supply-cerebral arterial thrombosis (ischemic stroke) and herpes zoster (HZ), although the causality remains unclear. This study aims to explore the potential causal link in relation to ischemic stroke and HZ. We performed a Mendelian randomization analysis (MR). Our objective is to provide fresh perspectives for the clinical prevention of ischemic stroke in individuals with HZ. Data from the European Molecular Biology Laboratory were utilized in the genome-wide association study (GWAS) of ischemic stroke. The study included data from 484,121 participants, with the FinnGen Consortium contributing data for zoster outcomes (n_case = 2080; n_control = 211,856), primarily focusing on European population samples. We conducted a comparative analysis of figures from the GWAS for ischemic stroke alongside that for zoster within a MR framework. Employing inverse variance weighting as our primary method of analysis, we undertook a thorough investigation into the potential causal relationship between ischemic stroke and zoster. Additionally, we adopted complementary approaches, including maximum likelihood estimation, MR-Egger, weighted median, and MR-Polyvalent Residuals and Outliers method to provide a comprehensive assessment of causality. To examine the variability among the instrumental variables, we utilized Cochran's Q statistic as a key indicator. The analysis weighted by inverse variance indicated a significant impact of ischemic stroke on zoster within the zoster GWAS databases, yielding an odds ratio (OR) of 1.463 (95% confidence interval [CI]: 1.001-2.138; P value = 0.04). However, the MR-Egger analysis failed to yield substantial evidence for this relationship, presenting an OR of 0.599 (95% CI: 0.129-2.773; P value = 0.52).Similarly, the weighted median analysis failed to offer compelling endorsement of the association between ischemic stroke and zoster incidence, reporting an OR of 1.15 (95% CI: 0.736-1.806; P = 0.53). The implications of the MR analysis demonstrate a causal linkage between ischemic stroke and zoster.