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Title: Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆.
Austin Authors: 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;Cole, J W;McArdle, P F;Broderick, J P;Jimenez-Conde, J;Jern, C;Kissela, B M;Kleindorfer, D O;Lemmens, R;Meschia, J F;Rosand, J;Rundek, T;Sacco, R L;Schmidt, R;Sharma, P;Slowik, A;Thijs, Vincent N ;Woo, D;Worrall, B B;Kittner, S J;Petersson, J;Golland, P;Wu, O;Rost, N S;Lindgren, A
Affiliation: The Florey Institute of Neuroscience and Mental Health
Department of Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain
Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Department of Neurosciences, Experimental Neurology, VIB Center for Brain & Disease Research, Department of Neurology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
Henry and Allison McCance Center for Brain Health Massachusetts General Hospital, Boston, USA
Department of Neurology, Miller School of Medicine, University of Miami, The Evelyn F. McKnight Brain Institute, FL, USA
Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Austria
Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, United Kingdom
Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville, VA, USA
Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, USA
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, USA
Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden
Section of Neurology, Skåne University Hospital, Malmö, Sweden
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA
Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden
Issue Date: Aug-2022
Date: 2022-05-13
Publication information: Journal of Stroke and Cerebrovascular Diseases 2022; 31(8): 106546
Abstract: 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. 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. 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. 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.
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106546
ORCID: 0000-0002-6614-8417
Journal: Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
PubMed URL: 35576861
PubMed URL:
Type: Journal Article
Subjects: Common genetic variants
MRI phenotype
Posterior circulation ischemic stroke
Appears in Collections:Journal articles

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