Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆
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Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆. / 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, V; Woo, D; Worrall, B B; Kittner, S J; Petersson, J; Golland, P; Wu, O; Rost, N S; Lindgren, A.
In: J STROKE CEREBROVASC, Vol. 31, No. 8, 106546, 08.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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 - Diffusion Magnetic Resonance Imaging
KW - Humans
KW - Ischemic Stroke
KW - Migraine with Aura/diagnostic imaging
KW - Migraine without Aura/diagnostic imaging
KW - Risk Factors
U2 - 10.1016/j.jstrokecerebrovasdis.2022.106546
DO - 10.1016/j.jstrokecerebrovasdis.2022.106546
M3 - SCORING: Journal article
C2 - 35576861
VL - 31
JO - J STROKE CEREBROVASC
JF - J STROKE CEREBROVASC
SN - 1052-3057
IS - 8
M1 - 106546
ER -
