Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆
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1-s2.0-S1052305722002403-main.pdf
Description
Published version
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411.85 KB
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Adobe PDF
Checksum (MD5)
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Author(s)
Golland, Polina
Date Issued
August 2022
Journal
Journal of Stroke and Cerebrovascular Diseases
Publisher
Elsevier BV
Citation
Golland, Polina. 2022. "Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆." Journal of Stroke and Cerebrovascular Diseases, 31 (8).
Version
Final published version
Abstract
OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106546
