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Nat Genet. 2015 Jan;47(1):78-83. doi: 10.1038/ng.3154. Epub 2014 Nov 24.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Author information

1
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.
2
1] Centre National de Génotypage, Evry, France. [2] Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France. [3] Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
3
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
4
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
5
INSERM U897, University of Bordeaux, Bordeaux, France.
6
Department of Neurology, Basel University Hospital, Basel, Switzerland.
7
Department of Clinical and Experimental Sciences, Neurology Clinic, Brescia University Hospital, Brescia, Italy.
8
1] Department of Neurology, Leuven University Hospital, Leuven, Belgium. [2] Vesalius Research Center, VIB, Leuven, Belgium.
9
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
10
1] Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
11
1] INSERM U897, University of Bordeaux, Bordeaux, France. [2] Department of Statistical Genetics, Max Planck Institute for Psychiatry, Munich, Germany.
12
Department of Neurology, University Hospital of Münster, Münster, Germany.
13
1] Department of Neurology, University Hospital of Sainte-Anne, Paris, France. [2] Department of Neurology, University Hospital of Caen, Caen, France.
14
Department of Neurology, University of Virginia, Charlottesville, Virginia, USA.
15
Urgences Cérébro-Vasculaire, Assistance Publique-Hôpitaux de Paris Salpêtrière Urgences Cérébro-Vasculaires and Université Pierre et Marie Curie Paris Paris VI Université, Paris, France.
16
Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.
17
Department of Neurology, Dijon University Hospital, Dijon, France.
18
1] Stroke Unit, University of Perugia Santa Maria della Misericordia Hospital, Sant'Andrea delle Fratte, Perugia, Italy. [2] Division of Cardiovascular Medicine, University of Perugia Santa Maria della Misericordia Hospital, Sant'Andrea delle Fratte, Perugia, Italy.
19
Department of Cerebrovascular Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
20
Department of Neurology, Milan, San Raffaele University Hospital, Milan, Italy.
21
Maryland Stroke Center, Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
22
Department of Neurology, Amiens University Hospital, Amiens, France.
23
Department of Neurology, Besançon University Hospital, Besançon, France.
24
Department of Neurology, University of Milano Bicocca, San Gerardo Hospital, Monza, Italy.
25
Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
26
Department of Neurology, Lausanne University Hospital, Lausanne, Switzerland.
27
Division of Vascular Neurology, Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
28
1] Institute of Cardiovascular Research Royal Holloway University of London (ICR2UL), London, UK. [2] Ashford and St Peter's Hospitals, London, UK.
29
Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
30
1] Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia. [2] Centre for Cognition and Decision Making, Higher School of Economics, Moscow, Russia.
31
Center for Neurological Vascular Diagnostics, Munich, Germany.
32
Department of Neurology, Nantes University Hospital, Nantes, France.
33
Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
34
1] Stroke Pharmacogenomics and Genetics, Fundació Docència i Recerca MutuaTerrassa, Terrassa, Spain. [2] Laboratorio Neurovascular, Institut de Recerca, Hospital Vall d'Hebron, Barcelona, Spain.
35
Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
36
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
37
Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
38
Department of Rehabilitation, Schmieder Klinik, Heidelberg, Germany.
39
Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany.
40
Institute of Genetic Epidemiology, Helmholtz Center Munich, Neuherberg, Germany.
41
National Heart, Lung, and Blood Institute's Framingham Heart Study Cardiovascular Epidemiology and Human Genomics Branch, Framingham, Massachusetts, USA.
42
Department of Neurology, Rostock University Hospital, Rostock, Germany.
43
Department of Clinical and Experimental Sciences, Clinica Medica, Brescia University Hospital, Brescia, Italy.
44
Department of Epidemiology and Public Health, EA 3430, Strasbourg University, Strasbourg, France.
45
1] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [3] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [4] Netherlands Consortium for Healthy Aging, Leiden, the Netherlands.
46
1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
47
Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.
48
Institute of Experimental Medicine, University of Kiel, Kiel, Germany.
49
1] Department of Neurology, University of Virginia, Charlottesville, Virginia, USA. [2] Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
50
Centre National de Génotypage, Evry, France.
51
1] Centre National de Génotypage, Evry, France. [2] Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France. [3] Génome Québec, McGill University, Montreal, Quebec, Canada.
52
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.
53
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.
54
1] INSERM U744, Lille, France. [2] Institut Pasteur de Lille, Lille, France. [3] Université Lille Nord de France, Lille, France.

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.

PMID:
25420145
PMCID:
PMC5824623
DOI:
10.1038/ng.3154
[Indexed for MEDLINE]
Free PMC Article

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