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https://ahro.austin.org.au/austinjspui/handle/1/27441| Title: | Genome-wide association study identifies first locus associated with susceptibility to cerebral venous thrombosis. | Austin Authors: | Ken-Dror, Gie;Cotlarciuc, Ioana;Martinelli, Ida;Grandone, Elvira;Hiltunen, Sini;Lindgren, Erik;Margaglione, Maurizio;Duchez, Veronique Le Cam;Triquenot, Aude Bagan;Zedde, Marialuisa;Mancuso, Michelangelo;Ruigrok, Ynte M;Marjot, Thomas;Worrall, Brad;Majersik, Jennifer J;Metso, Tiina M;Putaala, Jukka;Haapaniemi, Elena;Zuurbier, Susanna M;Brouwer, Matthijs C;Passamonti, Serena M;Abbattista, Maria;Bucciarelli, Paolo;Mitchell, Braxton D;Kittner, Steven J;Lemmens, Robin;Jern, Christina;Pappalardo, Emanuela;Costa, Paolo;Colombi, Marina;de Sousa, Diana Aguiar;Rodrigues, Sofia;Canhão, Patrícia;Tkach, Aleksander;Santacroce, Rosa;Favuzzi, Giovanni;Arauz, Antonio;Colaizzo, Donatella;Spengos, Kostas;Hodge, Amanda;Ditta, Reina;Pezzini, Alessandro;Debette, Stephanie;Coutinho, Jonathan M;Thijs, Vincent N ;Jood, Katarina;Pare, Guillaume;Tatlisumak, Turgut;Ferro, José M;Sharma, Pankaj | Affiliation: | Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy Ob/Gyn Dept. The First I.M. Sechenov Moscow State Medical University 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 Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Neurology, Veterans Affairs Medical Center, Baltimore, Maryland, USA KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology; VIB Center for Brain & Disease Research, University Hospitals Leuven, Department of Neurology, Leuven, Belgium Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden Medical Genetics, Dept. of Clinical and Experimental Medicine, University of Foggia, Italy Normandie University, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit and Inserm CIC-CRB 1404, F 76000, Rouen, France Rouen University Hospital, Department of Neurology, F 76000, Rouen, France Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Italy UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, the Netherlands Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Department of Neurology, University of Virginia, Charlottesville, Virginia, USA Department of Neurology, University of Utah, Salt Lake City, Utah, USA Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, the Netherlands Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal Stroke Clinic, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico Department of Neurology, University of Athens School of Medicine, Eginition Hospital, Athens, Greece McMaster University, Pathology and Molecular Medicine. Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Ontario, Canada Department of Neurology, Bordeaux University Hospital, Bordeaux University, France Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan, Italy Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK 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 Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Neurology, Veterans Affairs Medical Center, Baltimore, Maryland, USA Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy Ob/Gyn Dept. The First I.M. Sechenov Moscow State Medical University Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan, Italy Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland Medical Genetics, Dept. of Clinical and Experimental Medicine, University of Foggia, Italy Normandie University, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit and Inserm CIC-CRB 1404, F 76000, Rouen, France Rouen University Hospital, Department of Neurology, F 76000, Rouen, France Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Italy UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, the Netherlands Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Department of Neurology, University of Virginia, Charlottesville, Virginia, USA Department of Neurology, University of Utah, Salt Lake City, Utah, USA Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, the Netherlands A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan, Italy KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology; VIB Center for Brain & Disease Research, University Hospitals Leuven, Department of Neurology, Leuven, Belgium A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan, Italy Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Italy Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal Department of Neurology, University of Utah, Salt Lake City, Utah, USA Medical Genetics, Dept. of Clinical and Experimental Medicine, University of Foggia, Italy Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy Stroke Clinic, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico Atherosclerosis and Thrombosis Unit, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy Department of Neurology, University of Athens School of Medicine, Eginition Hospital, Athens, Greece McMaster University, Pathology and Molecular Medicine. Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Ontario, Canada Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Italy Department of Neurology, Bordeaux University Hospital, Bordeaux University, France Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, the Netherlands McMaster University, Pathology and Molecular Medicine. Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Ontario, Canada Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal |
Issue Date: | Nov-2021 | Date: | 2021-08-30 | Publication information: | Annals of neurology 2021; 90(5): 777-788 | Abstract: | 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. Genome-wide association study performed to identify genetic variants influencing susceptibility to CVT. A two-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1205 ethnicity-matched control subjects divided into discovery and independent replication datasets. In the overall case-control cohort, we identified highly significant associations with 37 SNPs within 9q34.2 region. The strongest association was with rs8176645 (combined P = 9.15 × 10-24 ; OR = 2.01, 95%CI: 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95%CI: 2.21-3.20, P = 2.00 × 10-16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B or AB, were at 2.85 times (95%CI: 2.32-3.52, P = 2.00 × 10-16 ) increased risk of CVT compared with individuals with blood group-O. 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. This article is protected by copyright. All rights reserved. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/27441 | DOI: | 10.1002/ana.26205 | ORCID: | 0000-0003-3747-7112 | Journal: | Annals of Neurology | PubMed URL: | 34459509 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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