Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.

Adult Genetic Predisposition to Disease / genetics Genome-Wide Association Study Humans Intracranial Thrombosis / genetics Male Middle Aged Risk Factors Thrombophilia / genetics Venous Thrombosis / genetics

Journal

Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449

Informations de publication

Date de publication:
11 2021
Historique:
revised: 23 08 2021
received: 08 04 2021
accepted: 23 08 2021
pubmed: 31 8 2021
medline: 15 12 2021
entrez: 30 8 2021
Statut: ppublish

Résumé

Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10 We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.

Identifiants

DOI: 10.1002/ana.26205 PMID: 34459509 PMC: PMC8666091
pubmed: 34459509
doi: 10.1002/ana.26205
pmc: PMC8666091
mid: NIHMS1736731
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

777-788

Subventions

Organisme : the Interreg 2 Seas programme
Organisme : Dept of Health
Organisme : The Stroke Association
Organisme : NINDS NIH HHS
ID : R01 NS100178
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS114045
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105150
Pays : United States
Organisme : Dowager Countess Eleanor Peel Trust
Organisme : BLRD VA
ID : I01 BX004672
Pays : United States

Informations de copyright

© 2021 American Neurological Association.

Références

Stroke. 2016 Feb;47(2):307-16
pubmed: 26732560
Stroke. 2004 Mar;35(3):664-70
pubmed: 14976332
Nat Rev Genet. 2008 Jun;9(6):477-85
pubmed: 18427557
Blood. 2019 Nov 7;134(19):1645-1657
pubmed: 31420334
Diabetes. 2019 Dec;68(12):2327-2336
pubmed: 31537524
N Engl J Med. 2005 Apr 28;352(17):1791-8
pubmed: 15858188
Nat Commun. 2020 Jan 9;11(1):163
pubmed: 31919418
Stroke. 1996 Oct;27(10):1721-3
pubmed: 8841317
JAMA Neurol. 2019 Dec 1;76(12):1457-1465
pubmed: 31479105
Stroke. 2014 Jan;45(1):24-36
pubmed: 24262325
Blood. 2009 May 21;113(21):5298-303
pubmed: 19278955
Hum Mol Genet. 2016 May 1;25(9):1867-74
pubmed: 26908601
BMJ Open. 2016 Nov 22;6(11):e012351
pubmed: 27881526
Am J Hum Genet. 2005 Mar;76(3):449-62
pubmed: 15700229
Stat Med. 2002 Jun 15;21(11):1539-58
pubmed: 12111919
Semin Thromb Hemost. 2016 Sep;42(6):622-31
pubmed: 27272966
Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):830-838
pubmed: 31969017
Nature. 2012 Sep 20;489(7416):443-6
pubmed: 22895189
Genet Epidemiol. 2016 Apr;40(3):188-201
pubmed: 27027514
Diabetes. 2017 Nov;66(11):2888-2902
pubmed: 28566273
PLoS Genet. 2009 Mar;5(3):e1000421
pubmed: 19300482
Hum Mol Genet. 2014 Mar 1;23(5):1387-98
pubmed: 24163127
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Blood Transfus. 2014 Jan;12 Suppl 1:s337-42
pubmed: 23399370
Nat Rev Genet. 2010 Jul;11(7):459-63
pubmed: 20548291
Lancet. 1969 Mar 15;1(7594):539-42
pubmed: 4179835
Front Aging Neurosci. 2018 Jan 30;10:2
pubmed: 29441008
Nat Commun. 2018 Jan 15;9(1):224
pubmed: 29335400
Nat Genet. 2009 Sep;41(9):986-90
pubmed: 19648918
Stroke. 2011 Apr;42(4):913-8
pubmed: 21350198
PLoS One. 2016 Mar 31;11(3):e0151607
pubmed: 27031503
PLoS Genet. 2008 May 09;4(5):e1000072
pubmed: 18464913
Nat Protoc. 2014 Nov;9(11):2643-62
pubmed: 25321409
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Nat Genet. 2019 Nov;51(11):1574-1579
pubmed: 31676865
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Stroke. 2014 May;45(5):1338-41
pubmed: 24699058

Auteurs

Gie Ken-Dror (G)

Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK.
ORCID: 0000-0003-3747-7112

Ioana Cotlarciuc (I)

Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK.

Ida Martinelli (I)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Elvira Grandone (E)

Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Home for the Relief of Suffering, S. Giovanni Rotondo, Foggia, Italy.
Obstetrics/Gynecology Department, First I. M. Sechenov Moscow State Medical University, Moscow, Russia.

Sini Hiltunen (S)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Erik Lindgren (E)

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Maurizio Margaglione (M)

Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Veronique Le Cam Duchez (VLC)

Normandy University, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit and INSERM CIC-CRB 1404, Rouen, France.

Aude Bagan Triquenot (AB)

Department of Neurology, Rouen University Hospital, Rouen, France.

Marialuisa Zedde (M)

Neurology Unit, Stroke Unit, Local Health Unit-IRCCS of Reggio Emilia, Reggio Emilia, Italy.

Michelangelo Mancuso (M)

Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Italy.

Ynte M Ruigrok (YM)

UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands.

Thomas Marjot (T)

Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Brad Worrall (B)

Department of Neurology, University of Virginia, Charlottesville, VA.

Jennifer J Majersik (JJ)

Department of Neurology, University of Utah, Salt Lake City, UT.

Tiina M Metso (TM)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Jukka Putaala (J)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Elena Haapaniemi (E)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Susanna M Zuurbier (SM)

Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.

Matthijs C Brouwer (MC)

Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.

Serena M Passamonti (SM)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Maria Abbattista (M)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Paolo Bucciarelli (P)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Braxton D Mitchell (BD)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD.

Steven J Kittner (SJ)

Department of Neurology, University of Maryland School of Medicine, Baltimore, MD.
Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD.

Robin Lemmens (R)

Department of Neurosciences, Experimental Neurology, KU Leuven-University of Leuven; VIB Center for Brain & Disease Research; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.

Christina Jern (C)

Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.

Emanuela Pappalardo (E)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Paolo Costa (P)

Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.

Marina Colombi (M)

Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.

Diana Aguiar de Sousa (DA)

Department of Neurosciences, Hospital of Santa Maria, University of Lisbon, Lisbon, Portugal.

Sofia Rodrigues (S)

Department of Neurosciences, Hospital of Santa Maria, University of Lisbon, Lisbon, Portugal.

Patrícia Canhão (P)

Department of Neurosciences, Hospital of Santa Maria, University of Lisbon, Lisbon, Portugal.

Aleksander Tkach (A)

Department of Neurology, University of Utah, Salt Lake City, UT.

Rosa Santacroce (R)

Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Giovanni Favuzzi (G)

Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Home for the Relief of Suffering, S. Giovanni Rotondo, Foggia, Italy.

Antonio Arauz (A)

Stroke Clinic, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico.

Donatella Colaizzo (D)

Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Home for the Relief of Suffering, S. Giovanni Rotondo, Foggia, Italy.

Kostas Spengos (K)

Department of Neurology, University of Athens School of Medicine, Eginition Hospital, Athens, Greece.

Amanda Hodge (A)

McMaster University, Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Reina Ditta (R)

McMaster University, Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Alessandro Pezzini (A)

Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.

Stephanie Debette (S)

Department of Neurology, Bordeaux University Hospital, Bordeaux University, Bordeaux, France.

Jonathan M Coutinho (JM)

Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.

Vincent Thijs (V)

Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia.

Katarina Jood (K)

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Guillaume Pare (G)

McMaster University, Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Turgut Tatlisumak (T)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.

José M Ferro (JM)

Department of Neurosciences, Hospital of Santa Maria, University of Lisbon, Lisbon, Portugal.

Pankaj Sharma (P)

Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK.
Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London, UK.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thromboembolie › Embolie et thrombose intracrâniennes › Thrombose intracrânienne › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Thrombophilie › Genome-Wide Association Study Identifies First...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thrombose › Thrombose veineuse › Genome-Wide Association Study Identifies First...