title: Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.
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.
authors.affiliation: 1] INSERM U744, Lille, France. [2] Institut Pasteur de Lille, Lille, France. [3] Université Lille Nord de France, Lille, France. [4] Lille University Hospital, Lille, France. [5] Department of Neurology, Equipe d'accueil 1046, Lille, France. [6] INSERM U897, University of Bordeaux, Bordeaux, France.
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authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
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authors.initials: TM
authors.lastname: Metso
authors.affiliation: Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Manja
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authors.affiliation: INSERM U897, University of Bordeaux, Bordeaux, France.
authors.forename: Ganesh
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authors.affiliation: Department of Neurology, Basel University Hospital, Basel, Switzerland.
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authors.affiliation: Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.
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authors.affiliation: Department of Cerebrovascular Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
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authors.lastname: Lathrop
authors.affiliation: 1] Université Lille Nord de France, Lille, France. [2] Lille University Hospital, Lille, France. [3] Department of Neurology, Equipe d'accueil 1046, Lille, France. [4] INSERM U897, University of Bordeaux, Bordeaux, France.
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authors.lastname: Leys
authors.affiliation: 1] INSERM U744, Lille, France. [2] Institut Pasteur de Lille, Lille, France. [3] Université Lille Nord de France, Lille, France. [4] Lille University Hospital, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: 1] INSERM U744, Lille, France. [2] Institut Pasteur de Lille, Lille, France. [3] Université Lille Nord de France, Lille, France.
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mesh_terms: D000328:Adult; D000483:Alleles; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics; D020215:Carotid Artery, Internal, Dissection / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008881:Migraine Disorders / Q000453:epidemiology; D009203:Myocardial Infarction / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020217:Vertebral Artery Dissection / Q000453:epidemiology / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human