@article{2c9592897d4649d6afdadd5cffb20110,
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 = "Funding Information: Dr. N. Rost is in part supported by the NINDS R01NS0869051 (MRI-GENIE study, Principal Investigator), R01NS082285 (SALVO study, Principal Investigator) and U19NS115388 (DISCOVERY study, Principal Investigator) jointly funded by NINDS and National Institute on Aging. Funding Information: Dr. C. Jern: Receives funding from the Swedish Research Council (2018-02543), the Swedish Heart and Lung Foundation (20190203), and the Swedish State under the agreement between the Swedish government and the county councils (the ALF-agreement; ALFGBG-720081). Funding Information: Dr. B. Mitchell: The National Institute of Neurological Disorders and Stroke – Stroke Genetics Network (NINDS-SIGN) study was funded by the US National Institute of Neurological Disorders and Stroke, National Institutes of Health (U01 NS069208 and R01 NS100178). Funding Information: Dr. J. Rosand; Research support by NIH, American Heart Association and OneMind. Funding Information: Dr. S. J. Kittner's effort on this project was supported in part by VA RR&D BX004672-01A1, and the following NINDS awards: R01NS086905, U18NS115388, R01NS100178, and R01NS105150. Funding Information: Dr. J. F. Meschia receives funding from the US National Institutes of Health National Institutes of Neurological Disorders and Stroke (NIH NINDS) for serving as co-Principal Investigator for the Clinical Coordinating Center of the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2; U01NS080168) and for serving as the Recruitment and Retention Core Lead of the Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY (DISCOVERY; U19NS115388). Funding Information: Dr P. Sharma: BRAINS is funded by the Henry Smith Charity, UK-India Education Research initiative, Qatar National Research Foundation; PS was personally funded by a Dept of Health Senior Fellowship program. Funding Information: Dr. E. Giralt-Steinhauer received funding from Instituto de Salud Carlos III, with a Grant (JR18/00004). Funding Information: Dr. J. Roquer: Supported in part by Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III FEDER, RD16/0019/0002. INVICTUS-PLUS). 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",
}