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Migraine and Ischemic Stroke: A Mendelian Randomization Study
Mei-Jun Shu1, Jia-Rui Li2, Yi-Cheng Zhu1
1Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Beijing, 10073, China.
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.
Insights
This study found no causal link between migraine and ischemic stroke or its subtypes. Mendelian randomization analysis of genetic data did not support a causal relationship, strengthening evidence for independent conditions.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Previous studies suggest a link between migraine and increased ischemic stroke risk.
- However, robust evidence for a causal relationship is limited.
- This study investigates the potential causal link between migraine and ischemic stroke, including its subtypes.
Purpose of the Study:
- To explore the potential causal relationship between migraine and ischemic stroke.
- To investigate the causal association with specific ischemic stroke subtypes: large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES).
Main Methods:
- Utilized genome-wide association study (GWAS) data for migraine in European ancestries.
- Employed two-sample Mendelian randomization (MR) analysis with inverse-variance-weighted method.
- Conducted sensitivity analyses using MR-Egger, weighted median, and other methods for robustness.
Main Results:
- No statistically significant causal association was detected between migraine and overall ischemic stroke (P=0.159).
- Similarly, no significant causal links were found for large artery stroke (P=0.018), small vessel stroke (P=0.460), or cardioembolic stroke (P=0.850).
- Sensitivity analyses confirmed the consistency of these findings.
Conclusions:
- This Mendelian randomization study provides evidence against a causal effect of migraine on ischemic stroke.
- The findings suggest that migraine and ischemic stroke may be independent conditions.
- Further research may explore shared risk factors or alternative biological pathways.
