Migraine Genetic Variants Influence Cerebral Blood Flow

• Published in: Headache 2020-01, Vol.60 (1), p.90-100
• Main Authors: Knol, Maria J., Loehrer, Elizabeth A., Wen, Ke‐xin, Bos, Daniel, Ikram, M. Kamran, Vernooij, Meike W., Adams, Hieab H.H., Ikram, M. Arfan
• Format: Article
• Language: English
• Subjects: Aged; Basilar Artery - diagnostic imaging; Basilar Artery - physiopathology; Blood flow; brain imaging; Carotid Arteries - drug effects; Carotid Arteries - physiopathology; Cerebral blood flow; cerebrovascular circulation; Cerebrovascular Circulation - genetics; Cerebrovascular Circulation - physiology; Cluster analysis; Clustering; Cohort Studies; Female; Flow velocity; Genetic Association Studies; Genetic diversity; Genetic factors; Genetic Predisposition to Disease - genetics; Genetic variance; Genetic Variation; genetics; Genome-wide association studies; Genomes; Headache; Hemodynamics; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Migraine; migraine disorders; Migraine Disorders - diagnostic imaging; Migraine Disorders - genetics; Migraine Disorders - physiopathology; Netherlands; Neuroimaging; perfusion imaging; Population studies; regional blood flow; Regression analysis; Regression models; Research Submission; Research Submissions
• ISSN: 0017-8748; 1526-4610
• DOI: 10.1111/head.13651

Objective To investigate the association of migraine genetic variants with cerebral blood flow (CBF). Background Migraine is a common disorder with many genetic and non‐genetic factors affecting its occurrence. The exact pathophysiological mechanisms underlying the disease remain unclear, but are known to involve hemodynamic and vascular disruptions. Recent genome‐wide association studies have identified 44 genetic variants in 38 genetic loci that affect the risk of migraine, which provide the opportunity to further disentangle these mechanisms. Methods We included 4665 participants of the population‐based Rotterdam Study (mean age 65.0 ± 10.9 years, 55.6% women). Cross‐sectional area (mm2), flow velocity (mm/s), and blood flow (mL/min) were measured in both carotids and the basilar artery using 2‐dimensional phase‐contrast magnetic resonance imaging. We analyzed 43 previously identified migraine variants separately and calculated a genetic risk score (GRS). To assess the association with CBF, we used linear regression models adjusted for age, sex, and total brain volume. Hierarchical clustering was performed based on the associations with CBF measures and tissue enrichment. Results The rs67338227 risk allele was associated with higher flow velocity and smaller cross‐sectional area in the carotids (Pminimum = 3.7 × 10−8). Other variants were related to CBF with opposite directions of effect, but not significantly after multiple testing adjustments (P