1. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.
- Author
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Debette S, Kamatani Y, Metso TM, Kloss M, Chauhan G, Engelter ST, Pezzini A, Thijs V, Markus HS, Dichgans M, Wolf C, Dittrich R, Touzé E, Southerland AM, Samson Y, Abboud S, Béjot Y, Caso V, Bersano A, Gschwendtner A, Sessa M, Cole J, Lamy C, Medeiros E, Beretta S, Bonati LH, Grau AJ, Michel P, Majersik JJ, Sharma P, Kalashnikova L, Nazarova M, Dobrynina L, Bartels E, Guillon B, van den Herik EG, Fernandez-Cadenas I, Jood K, Nalls MA, De Leeuw FE, Jern C, Cheng YC, Werner I, Metso AJ, Lichy C, Lyrer PA, Brandt T, Boncoraglio GB, Wichmann HE, Gieger C, Johnson AD, Böttcher T, Castellano M, Arveiler D, Ikram MA, Breteler MM, Padovani A, Meschia JF, Kuhlenbäumer G, Rolfs A, Worrall BB, Ringelstein EB, Zelenika D, Tatlisumak T, Lathrop M, Leys D, Amouyel P, and Dallongeville J
- Subjects
- Adult, Brain Ischemia epidemiology, Brain Ischemia genetics, Carotid Artery, Internal, Dissection epidemiology, Female, Finland epidemiology, Follow-Up Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypercholesterolemia epidemiology, Hypertension epidemiology, Male, Microfilament Proteins physiology, Middle Aged, Migraine Disorders epidemiology, Myocardial Infarction epidemiology, Obesity epidemiology, Odds Ratio, Risk Factors, Vertebral Artery Dissection epidemiology, Alleles, Carotid Artery, Internal, Dissection genetics, Microfilament Proteins genetics, Polymorphism, Single Nucleotide, Vertebral Artery Dissection genetics
- Abstract
Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
- Published
- 2015
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