Migraine and Early-onset Ischemic Stroke: A Mendelian Randomization Study

Abstract

Objective: Through the utilization of the data specifically related to early-onset ischemic stroke, we aimed to investigate the causal effects of migraine and its subtypes on the risk of early-onset ischemic stroke using the two-sample Mendelian randomization method. Methods: Genetic instrumental variables were acquired from two sources with the largest sample sizes available. Summary data for early-onset ischemic stroke was acquired from a study encompassing individuals aged 18 to 59 years, comprising 16,730 cases and 599,237 non-stroke controls. The random-effects inverse variance weighted method was used as the primary analysis approach. Results: The Mendelian randomization analysis revealed no association between overall migraine and migraine without aura with the risk of early-onset ischemic stroke. However, migraine with aura showed a suggestive association with an elevated risk of early-onset ischemic stroke, with odds ratios of 1.114 (95% confidence interval = 1.005 to 1.236, p-value = 0.040) and 1.062 (95% confidence interval = 1.002 to 1.126, p-value = 0.042) based on instruments from two independent sources. The odds ratio was 1.074 (95% confidence interval = 1.022 to 1.130, p-value = 0.005) based on instruments from both two sources. No evidence of heterogeneity or horizontal pleiotropy was found. Furthermore, a positive genetic correlation was found between migraine with aura and early-onset ischemic stroke (genetic correlation = 0.208, 95% confidence interval = 0.038 to 0.377, p-value = 0.016). By contrast, migraine with aura was not related to ischemic stroke of all adults. Conclusion: This study provides evidence of a causal relationship between migraine with aura and the risk of early-onset ischemic stroke.