Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆

P. Frid; H. Xu; B. D. Mitchell; M. Drake; J. Wasselius; B. Gaynor; K. Ryan; A. K. Giese; M. Schirmer; K. L. Donahue; R. Irie; M. J.R.J. Bouts; E. C. McIntosh; S. J.T. Mocking; A. V. Dalca; E. Giralt-Steinhauer; L. Holmegaard; K. Jood; J. Roquer; J. W. Cole; P. F. McArdle; J. P. Broderick; J. Jimenez-Conde; C. Jern; B. M. Kissela; D. O. Kleindorfer; R. Lemmens; J. F. Meschia; J. Rosand; T. Rundek; R. L. Sacco; R. Schmidt; P. Sharma; A. Slowik; V. Thijs; D. Woo; B. B. Worrall; S. J. Kittner; J. Petersson; P. Golland; O. Wu; N. S. Rost; A. Lindgren

doi:10.1016/j.jstrokecerebrovasdis.2022.106546

Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆

P. Frid, H. Xu, B. D. Mitchell, M. Drake, J. Wasselius, B. Gaynor, K. Ryan, A. K. Giese, M. Schirmer, K. L. Donahue, R. Irie, M. J.R.J. Bouts, E. C. McIntosh, S. J.T. Mocking, A. V. Dalca, E. Giralt-Steinhauer, L. Holmegaard, K. Jood, J. Roquer, J. W. ColeP. F. McArdle, J. P. Broderick, J. Jimenez-Conde, C. Jern, B. M. Kissela, D. O. Kleindorfer, R. Lemmens, J. F. Meschia, J. Rosand, T. Rundek, R. L. Sacco, R. Schmidt, P. Sharma, A. Slowik, V. Thijs, D. Woo, B. B. Worrall, S. J. Kittner, J. Petersson, P. Golland, O. Wu, N. S. Rost, A. Lindgren

Neurology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	106546
Journal	Journal of Stroke and Cerebrovascular Diseases
Volume	31
Issue number	8
DOIs	https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106546
State	Published - Aug 2022

Keywords

Common genetic variants
MRI phenotype
Migraine
Posterior circulation ischemic stroke

ASJC Scopus subject areas

Surgery
Rehabilitation
Clinical Neurology
Cardiology and Cardiovascular Medicine

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10.1016/j.jstrokecerebrovasdis.2022.106546

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Frid, P., Xu, H., Mitchell, B. D., Drake, M., Wasselius, J., Gaynor, B., Ryan, K., Giese, A. K., Schirmer, M., Donahue, K. L., Irie, R., Bouts, M. J. R. J., McIntosh, E. C., Mocking, S. J. T., Dalca, A. V., Giralt-Steinhauer, E., Holmegaard, L., Jood, K., Roquer, J., ... Lindgren, A. (2022). Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆. Journal of Stroke and Cerebrovascular Diseases, 31(8), Article 106546. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106546

Frid, P, Xu, H, Mitchell, BD, Drake, M, Wasselius, J, Gaynor, B, Ryan, K, Giese, AK, Schirmer, M, Donahue, KL, Irie, R, Bouts, MJRJ, McIntosh, EC, Mocking, SJT, Dalca, AV, Giralt-Steinhauer, E, Holmegaard, L, Jood, K, Roquer, J, Cole, JW, McArdle, PF, Broderick, JP, Jimenez-Conde, J, Jern, C, Kissela, BM, Kleindorfer, DO, Lemmens, R, Meschia, JF, Rosand, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Thijs, V, Woo, D, Worrall, BB, Kittner, SJ, Petersson, J, Golland, P, Wu, O, Rost, NS & Lindgren, A 2022, 'Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆', Journal of Stroke and Cerebrovascular Diseases, vol. 31, no. 8, 106546. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106546

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title = "Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆",

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.",

keywords = "Common genetic variants, MRI phenotype, Migraine, Posterior circulation ischemic stroke",

author = "P. Frid and H. Xu and Mitchell, {B. D.} and M. Drake and J. Wasselius and B. Gaynor and K. Ryan and Giese, {A. K.} and M. Schirmer and Donahue, {K. L.} and R. Irie and Bouts, {M. J.R.J.} and McIntosh, {E. C.} and Mocking, {S. J.T.} and Dalca, {A. V.} and E. Giralt-Steinhauer and L. Holmegaard and K. Jood and J. Roquer and Cole, {J. W.} and McArdle, {P. F.} and Broderick, {J. P.} and J. Jimenez-Conde and C. Jern and Kissela, {B. M.} and Kleindorfer, {D. O.} and R. Lemmens and Meschia, {J. F.} and J. Rosand and T. Rundek and Sacco, {R. L.} and R. Schmidt and P. Sharma and A. Slowik and V. Thijs and D. Woo and Worrall, {B. B.} and Kittner, {S. J.} and J. Petersson and P. Golland and O. Wu and Rost, {N. S.} and A. Lindgren",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = aug,

doi = "10.1016/j.jstrokecerebrovasdis.2022.106546",

language = "English (US)",

volume = "31",

journal = "Journal of Stroke and Cerebrovascular Diseases",

issn = "1052-3057",

publisher = "W.B. Saunders Ltd",

number = "8",

}

TY - JOUR

T1 - Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆

AU - Frid, P.

AU - Xu, H.

AU - Mitchell, B. D.

AU - Drake, M.

AU - Wasselius, J.

AU - Gaynor, B.

AU - Ryan, K.

AU - Giese, A. K.

AU - Schirmer, M.

AU - Donahue, K. L.

AU - Irie, R.

AU - Bouts, M. J.R.J.

AU - McIntosh, E. C.

AU - Mocking, S. J.T.

AU - Dalca, A. V.

AU - Giralt-Steinhauer, E.

AU - Holmegaard, L.

AU - Jood, K.

AU - Roquer, J.

AU - Cole, J. W.

AU - McArdle, P. F.

AU - Broderick, J. P.

AU - Jimenez-Conde, J.

AU - Jern, C.

AU - Kissela, B. M.

AU - Kleindorfer, D. O.

AU - Lemmens, R.

AU - Meschia, J. F.

AU - Rosand, J.

AU - Rundek, T.

AU - Sacco, R. L.

AU - Schmidt, R.

AU - Sharma, P.

AU - Slowik, A.

AU - Thijs, V.

AU - Woo, D.

AU - Worrall, B. B.

AU - Kittner, S. J.

AU - Petersson, J.

AU - Golland, P.

AU - Wu, O.

AU - Rost, N. S.

AU - Lindgren, A.

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

KW - Common genetic variants

KW - MRI phenotype

KW - Migraine

KW - Posterior circulation ischemic stroke

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UR - http://www.scopus.com/inward/citedby.url?scp=85129989944&partnerID=8YFLogxK

U2 - 10.1016/j.jstrokecerebrovasdis.2022.106546

DO - 10.1016/j.jstrokecerebrovasdis.2022.106546

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C2 - 35576861

AN - SCOPUS:85129989944

SN - 1052-3057

VL - 31

JO - Journal of Stroke and Cerebrovascular Diseases

JF - Journal of Stroke and Cerebrovascular Diseases

IS - 8

M1 - 106546

ER -

Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆

Abstract

Keywords

ASJC Scopus subject areas

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