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☆

J Stroke Cerebrovasc Dis. 2022 Aug;31(8):106546. doi: 10.1016/j.jstrokecerebrovasdis.2022.106546. Epub 2022 May 13.

Authors

P Frid¹, H Xu², B D Mitchell³, M Drake⁴, J Wasselius⁴, B Gaynor⁵, K Ryan⁵, A K Giese⁶, M Schirmer⁶, K L Donahue⁶, R Irie⁷, M J R J Bouts⁷, E C McIntosh⁷, S J T Mocking⁷, A V Dalca⁸, E Giralt-Steinhauer⁹, L Holmegaard¹⁰, K Jood¹⁰, J Roquer⁹, J W Cole¹¹, P F McArdle⁵, J P Broderick¹², J Jimenez-Conde⁹, C Jern¹³, B M Kissela¹², D O Kleindorfer¹², R Lemmens¹⁴, J F Meschia¹⁵, J Rosand¹⁶, T Rundek¹⁷, R L Sacco¹⁷, R Schmidt¹⁸, P Sharma¹⁹, A Slowik²⁰, V Thijs²¹, D Woo¹², B B Worrall²², S J Kittner¹¹, J Petersson²³, P Golland²⁴, O Wu⁷, N S Rost⁶, A Lindgren²⁵

Affiliations

¹ Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden; Section of Neurology, Skåne University Hospital, Malmö, Sweden. Electronic address: [email protected].
² Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: [email protected].
³ Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA.
⁴ Department of Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden; Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden.
⁵ Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁶ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
⁸ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, USA.
⁹ Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain.
¹⁰ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
¹² Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹³ Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁴ Department of Neurosciences, Experimental Neurology, VIB Center for Brain & Disease Research, Department of Neurology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
¹⁵ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹⁶ Henry and Allison McCance Center for Brain Health Massachusetts General Hospital, Boston, USA.
¹⁷ Department of Neurology, Miller School of Medicine, University of Miami, The Evelyn F. McKnight Brain Institute, FL, USA.
¹⁸ Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Austria.
¹⁹ Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, United Kingdom.
²⁰ Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.
²¹ Stroke Division, Florey Institute of Neuroscience and Mental Health, and Department of Neurology, Austin Health, Heidelberg, Australia.
²² Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
²³ Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.
²⁴ Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, USA.
²⁵ Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden; Section of Neurology, Skåne University Hospital, Lund, Sweden.

PMID: 35576861
PMCID: PMC10601407
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106546

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.

MeSH terms

Diffusion Magnetic Resonance Imaging
Humans
Ischemic Stroke*
Migraine with Aura* / diagnostic imaging
Migraine with Aura* / genetics
Migraine without Aura* / diagnostic imaging
Migraine without Aura* / genetics
Risk Factors

Abstract

MeSH terms

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