Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆
(2022) In Journal of Stroke and Cerebrovascular Diseases 31(8).- 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;... (More)
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.
(Less)
- author
- organization
- publishing date
- 2022-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Common genetic variants, Migraine, MRI phenotype, Posterior circulation ischemic stroke
- in
- Journal of Stroke and Cerebrovascular Diseases
- volume
- 31
- issue
- 8
- article number
- 106546
- publisher
- Elsevier
- external identifiers
-
- scopus:85129989944
- pmid:35576861
- ISSN
- 1052-3057
- DOI
- 10.1016/j.jstrokecerebrovasdis.2022.106546
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2022 The Authors
- id
- 28f9978f-e3e8-4318-b18f-664aa2bb2065
- date added to LUP
- 2022-08-18 13:27:19
- date last changed
- 2024-10-02 15:37:47
@article{28f9978f-e3e8-4318-b18f-664aa2bb2065,
abstract = {{<p>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.</p>}},
author = {{Frid, P. and Xu, H. and Mitchell, B. D. and Drake, M. and Wasselius, J. and Gaynor, B. and Ryan, K. and Giese, A. K. and Schirmer, M. and Donahue, K. L. and Irie, R. and Bouts, M. J.R.J. and McIntosh, E. C. and Mocking, S. J.T. and Dalca, A. V. and Giralt-Steinhauer, E. and Holmegaard, Lukas and Jood, K. and Roquer, J. and Cole, J. W. and McArdle, P. F. and Broderick, J. P. and Jimenez-Conde, J. and Jern, C. and Kissela, B. M. and Kleindorfer, D. O. and Lemmens, R. and Meschia, J. F. and Rosand, J. and Rundek, T. and Sacco, R. L. and Schmidt, R. and Sharma, P. and Slowik, A. and Thijs, V. and Woo, D. and Worrall, B. B. and Kittner, S. J. and Petersson, J. and Golland, P. and Wu, O. and Rost, N. S. and Lindgren, A.}},
issn = {{1052-3057}},
keywords = {{Common genetic variants; Migraine; MRI phenotype; Posterior circulation ischemic stroke}},
language = {{eng}},
number = {{8}},
publisher = {{Elsevier}},
series = {{Journal of Stroke and Cerebrovascular Diseases}},
title = {{Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆}},
url = {{http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2022.106546}},
doi = {{10.1016/j.jstrokecerebrovasdis.2022.106546}},
volume = {{31}},
year = {{2022}},
}