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

ObjectiveThrough 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. MethodsGenetic 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. ResultsThe 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. ConclusionThis study provides evidence of a causal relationship between migraine with aura and the risk of early-onset ischemic stroke.