Migraine and Ischemic Stroke: A Mendelian Randomization Study

INTRODUCTION: Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)]. METHODS: We used data on genetic variants associated with migraine identified from a genome-wide association study (GWAS) meta-analysis among 889,018 European ancestries. Summary data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium including up to 438,847 participants. We performed two-sample Mendelian randomization (MR) analyses using the inverse-variance-weighted method as the primary approach. The MR-Egger, weighted median, simple median, simple mode, and weighted mode methods were also conducted as sensitivity analyses to determine the robustness of our results. RESULTS: We failed to detect statistically significant associations between migraine and ischemic stroke (OR, 0.935; 95% CI 0.851–1.027; P = 0.159) and its subtypes (LAS: OR, 0.818; 95% CI 0.692–0.967; P = 0.018) (SVS: OR, 0.935; 95% CI 0.781–1.119; P = 0.460) (CES: OR, 1.015; 95% CI 0.867–1.189; P = 0.850). The results were consistent with the sensitivity analyses. CONCLUSIONS: By conducting a series of causal inference approaches, this study supports no causal effect of migraine on ischemic stroke and its subtypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-021-00310-y.