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

被引：175

作者：

Debette, Stephanie ^{[1
,2
,3
,4
,5
]}

Kamatani, Yoichiro ^{[6
,7
,8
]}

Metso, Tiina M. ^{[9
]}

Kloss, Manja ^{[10
]}

Chauhan, Ganesh ^{[5
]}

Engelter, Stefan T. ^{[11
]}

Pezzini, Alessandro ^{[12
]}

Thijs, Vincent ^{[13
,14
]}

Markus, Hugh S. ^{[15
]}

Dichgans, Martin ^{[16
,17
]}

Wolf, Christiane ^{[18
]}

Dittrich, Ralf ^{[19
]}

Touze, Emmanuel ^{[20
,21
]}

Southerland, Andrew M. ^{[22
]}

Samson, Yves ^{[23
]}

Abboud, Sherine ^{[24
]}

Bejot, Yannick ^{[25
]}

Caso, Valeria ^{[26
,27
]}

Bersano, Anna ^{[28
]}

Gschwendtner, Andreas ^{[16
,17
]}

Sessa, Maria ^{[29
]}

Cole, John ^{[30
]}

Lamy, Chantal ^{[31
]}

Medeiros, Elisabeth ^{[32
]}

Beretta, Simone ^{[33
]}

Bonati, Leo H.

Grau, Armin J. ^{[34
]}

Michel, Patrik ^{[35
]}

Majersik, Jennifer J. ^{[36
]}

Sharma, Pankaj ^{[37
,38
]}

Kalashnikova, Ludmila ^{[39
]}

Nazarova, Maria ^{[40
]}

Dobrynina, Larisa ^{[39
]}

Bartels, Eva ^{[41
]}

Guillon, Benoit ^{[42
]}

van den Herik, Evita G.

Fernandez-Cadenas, Israel ^{[44
,45
]}

Jood, Katarina ^{[46
]}

Nalls, Michael A. ^{[47
]}

De Leeuw, Frank-Erik ^{[48
]}

Jern, Christina ^{[48
]}

Cheng, Yu-Ching ^{[30
]}

Werner, Inge ^{[10
]}

Metso, Antti J. ^{[9
]}

Lichy, Christoph ^{[10
]}

Lyrer, Philippe A. ^{[11
]}

Brandt, Tobias ^{[49
]}

Boncoraglio, Giorgio B. ^{[28
]}

Wichmann, Heinz-Erich ^{[50
]}

Gieger, Christian ^{[51
]}

机构：

[1] INSERM, U744, F-59045 Lille, France

[2] Inst Pasteur, F-59019 Lille, France

[3] Lille Univ Hosp, Lille, France

[4] Dept Neurol, Equipe Accueil 1046, Lille, France

[5] Univ Bordeaux, INSERM, U897, Bordeaux, France

[6] Ctr Natl Genotypage, Evry, France

[7] CEPH, Fdn Jean Dausset, Paris, France

[8] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[9] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland

[10] Univ Heidelberg Hosp, Dept Neurol, Heidelberg, Germany

[11] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland

[12] Brescia Univ Hosp, Neurol Clin, Dept Clin & Expt Sci, Brescia, Italy

[13] Leuven Univ Hosp, Dept Neurol, Leuven, Belgium

[14] VIB, Vesalius Res Ctr, Leuven, Belgium

[15] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[16] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany

[17] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[18] Max Planck Inst Psychiat, Dept Stat Genet, D-80804 Munich, Germany

[19] Univ Hosp Munster, Dept Neurol, Munster, Germany

[20] Univ Hosp Sainte Anne, Dept Neurol, Paris, France

[21] Univ Hosp Caen, Dept Neurol, Caen, France

[22] Univ Virginia, Dept Neurol, Charlottesville, VA USA

[23] Assistance Publ Hop Paris Salpetriere Urgences Ce, Paris, France

[24] Univ Libre Bruxelles, Lab Expt Neurol, Brussels, Belgium

[25] Dijon Univ Hosp, Dept Neurol, Dijon, France

[26] Univ Perugia, Santa Maria Misericordia Hosp, Stroke Unit, SantAndrea Fratte, I-06100 Perugia, Italy

[27] Univ Perugia, Santa Maria Misericordia Hosp, Div Cardiovasc Med, SantAndrea Fratte, I-06100 Perugia, Italy

[28] Ist Neurol Carlo Besta, Fdn Ist Ricovero Cura Carattere Sci, Dept Cerebrovasc Dis, Milan, Italy

[29] San Raffaele Univ Hosp, Dept Neurol, Milan, Italy

[30] Univ Maryland, Sch Med, Dept Neurol, Maryland Stroke Ctr, Baltimore, MD 21201 USA

[31] Amiens Univ Hosp, Dept Neurol, Amiens, France

[32] Besancon Univ Hosp, Dept Neurol, Besancon, France

[33] Univ Milano Bicocca, San Gerardo Hosp, Dept Neurol, Monza, Italy

[34] Klinikum Ludwigshafen, Dept Neurol, Ludwigshafen, Germany

[35] Univ Lausanne Hosp, Dept Neurol, Lausanne, Switzerland

[36] Univ Utah, Dept Neurol, Divis Vasc Neurol, Salt Lake City, UT USA

[37] Royal Holloway Univ London ICR2UL, Inst Cardiovasc Res, London, England

[38] Ashford & St Peters Hosp, London, England

[39] Russian Acad Med Sci, Res Ctr Neurol, Moscow, Russia

[40] Higher Sch Econ, Ctr Cognit & Decis Making, Moscow, Russia

[41] Ctr Neurol Vasc Diagnost, Munich, Germany

[42] Nantes Univ Hosp, Dept Neurol, Nantes, France

[43] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands

[44] Fdn Docencia Recerca MutuaTerrassa, Terrassa, Spain

[45] Hosp Valle De Hebron, Inst Recerca, Lab Neurovasc, Barcelona, Spain

[46] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden

[47] NIA, Neurogenet Lab, Mol Genet Sect, NIH, Bethesda, MD 20892 USA

[48] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Donders Inst Brain,Cognit & Behav,Ctr Neurosci, NL-6525 ED Nijmegen, Netherlands

[49] Schmieder Klin, Dept Rehabil, Heidelberg, Germany

[50] Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany

来源：

NATURE GENETICS | 2015年 / 47卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; VASCULAR RISK-FACTORS; ISCHEMIC-STROKE; INTRACRANIAL ANEURYSM; AORTIC-ANEURYSMS; IDENTIFIES; LOCI; MIGRAINE; GENE; METAANALYSIS;

D O I：

10.1038/ng.3154

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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)(1). Minor cervical traumas, infection, migraine and hypertension are putative risk factors(1-3), and inverse associations with obesity and hypercholesterolemia are described(3,4). No confirmed genetic susceptibility factors have been identified using candidate gene approaches(5). We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR(1)) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction(6-9). Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

引用

页码：78 / +

页数：8

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