Migraine Genetic Variants Influence Cerebral Blood Flow. 2020

Maria J Knol, and Elizabeth A Loehrer, and Ke-Xin Wen, and Daniel Bos, and M Kamran Ikram, and Meike W Vernooij, and Hieab H H Adams, and M Arfan Ikram
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

To investigate the association of migraine genetic variants with cerebral blood flow (CBF). 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. 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. 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 < 1.4 × 10-4 ). The migraine GRS was not associated with CBF after multiple testing corrections. Migraine risk variants were found to be enriched for flow in the basilar artery (λ = 2.39). These findings show that genetic migraine risk is complexly associated with alterations in cerebral hemodynamics.

UI MeSH Term Description Entries
D008279 Magnetic Resonance Imaging Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. Chemical Shift Imaging,MR Tomography,MRI Scans,MRI, Functional,Magnetic Resonance Image,Magnetic Resonance Imaging, Functional,Magnetization Transfer Contrast Imaging,NMR Imaging,NMR Tomography,Tomography, NMR,Tomography, Proton Spin,fMRI,Functional Magnetic Resonance Imaging,Imaging, Chemical Shift,Proton Spin Tomography,Spin Echo Imaging,Steady-State Free Precession MRI,Tomography, MR,Zeugmatography,Chemical Shift Imagings,Echo Imaging, Spin,Echo Imagings, Spin,Functional MRI,Functional MRIs,Image, Magnetic Resonance,Imaging, Magnetic Resonance,Imaging, NMR,Imaging, Spin Echo,Imagings, Chemical Shift,Imagings, Spin Echo,MRI Scan,MRIs, Functional,Magnetic Resonance Images,Resonance Image, Magnetic,Scan, MRI,Scans, MRI,Shift Imaging, Chemical,Shift Imagings, Chemical,Spin Echo Imagings,Steady State Free Precession MRI
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008881 Migraine Disorders A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1) Acute Confusional Migraine,Headache, Migraine,Status Migrainosus,Abdominal Migraine,Cervical Migraine Syndrome,Hemicrania Migraine,Migraine,Migraine Headache,Migraine Variant,Sick Headache,Abdominal Migraines,Acute Confusional Migraines,Cervical Migraine Syndromes,Disorder, Migraine,Disorders, Migraine,Headache, Sick,Headaches, Migraine,Headaches, Sick,Hemicrania Migraines,Migraine Disorder,Migraine Headaches,Migraine Syndrome, Cervical,Migraine Syndromes, Cervical,Migraine Variants,Migraine, Abdominal,Migraine, Acute Confusional,Migraine, Hemicrania,Migraines,Migraines, Abdominal,Migraines, Acute Confusional,Migraines, Hemicrania,Sick Headaches,Variant, Migraine,Variants, Migraine
D009426 Netherlands Country located in EUROPE. It is bordered by the NORTH SEA, BELGIUM, and GERMANY. Constituent areas are Aruba, Curacao, and Sint Maarten, formerly included in the NETHERLANDS ANTILLES. Holland,Kingdom of the Netherlands
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D002560 Cerebrovascular Circulation The circulation of blood through the BLOOD VESSELS of the BRAIN. Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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