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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
Bakker, Mark K; van der Spek, Rick A A; van Rheenen, Wouter; Morel, Sandrine; Bourcier, Romain; Hostettler, Isabel C; Alg, Varinder S; van Eijk, Kristel R; Koido, Masaru; Akiyama, Masato; Terao, Chikashi; Matsuda, Koichi; Walters, Robin G; Lin, Kuang; Li, Liming; Millwood, Iona Y; Chen, Zhengming; Rouleau, Guy A; Zhou, Sirui; Rannikmäe, Kristiina; Sudlow, Cathie L M; Houlden, Henry; van den Berg, Leonard H; Dina, Christian; Naggara, Olivier; Gentric, Jean-Christophe; Shotar, Eimad; Eugène, François; Desal, Hubert; Winsvold, Bendik S; Børte, Sigrid; Johnsen, Marianne Bakke; Brumpton, Ben M; Sandvei, Marie Søfteland; Willer, Cristen J; Hveem, Kristian; Zwart, John-Anker; Verschuren, W M Monique; Friedrich, Christoph M; Hirsch, Sven; Schilling, Sabine; Dauvillier, Jérôme; Martin, Olivier; Jones, Gregory T; Bown, Matthew J; Ko, Nerissa U; Kim, Helen; Coleman, Jonathan R I; Breen, Gerome; Zaroff, Jonathan G.
Afiliación
  • Bakker MK; Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands. m.k.bakker-25@umcutrecht.nl.
  • van der Spek RAA; Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
  • van Rheenen W; Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
  • Morel S; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Bourcier R; Neurosurgery Division, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
  • Hostettler IC; l'institut du thorax Université de Nantes, CHU Nantes, INSERM, CNRS, Nantes, France.
  • Alg VS; CHU Nantes, Department of Neuroradiology, Nantes, France.
  • van Eijk KR; Stroke Research Centre, University College London Queen Square Institute of Neurology, London, UK.
  • Koido M; Department of Neurosurgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
  • Akiyama M; Stroke Research Centre, University College London Queen Square Institute of Neurology, London, UK.
  • Terao C; Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
  • Matsuda K; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Walters RG; Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Lin K; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Li L; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Millwood IY; Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Chen Z; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Rouleau GA; Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Zhou S; Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Rannikmäe K; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Sudlow CLM; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
  • Houlden H; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • van den Berg LH; Department of Epidemiology, School of Public Health, Peking University Health Science Center, Beijing, China.
  • Dina C; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Naggara O; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
  • Gentric JC; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Shotar E; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
  • Eugène F; Montréal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.
  • Desal H; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada.
  • Winsvold BS; Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Børte S; Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Johnsen MB; UK Biobank, Cheadle, Stockport, UK.
  • Brumpton BM; Neurogenetics Laboratory, The National Hospital of Neurology and Neurosurgery, London, UK.
  • Sandvei MS; Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
  • Willer CJ; l'institut du thorax Université de Nantes, CHU Nantes, INSERM, CNRS, Nantes, France.
  • Hveem K; Pediatric Radiology, Necker Hospital for Sick Children, Université Paris Descartes, Paris, France.
  • Zwart JA; Department of Neuroradiology, Sainte-Anne Hospital and Université Paris Descartes, INSERM UMR, S894, Paris, France.
  • Verschuren WMM; Department of Neuroradiology, University Hospital of Brest, Brest, France.
  • Friedrich CM; Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France.
  • Hirsch S; Department of Neuroradiology, University Hospital of Rennes, Rennes, France.
  • Schilling S; l'institut du thorax Université de Nantes, CHU Nantes, INSERM, CNRS, Nantes, France.
  • Dauvillier J; CHU Nantes, Department of Neuroradiology, Nantes, France.
  • Martin O; Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
  • Jones GT; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Bown MJ; Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Ko NU; The Cancer Clinic, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Kim H; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Coleman JRI; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Breen G; HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Zaroff JG; Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
Nat Genet ; 52(12): 1303-1313, 2020 12.
Article en En | MEDLINE | ID: mdl-33199917
ABSTRACT
Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemorragia Subaracnoidea / Fumar / Aneurisma Intracraneal / Predisposición Genética a la Enfermedad / Hipertensión Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemorragia Subaracnoidea / Fumar / Aneurisma Intracraneal / Predisposición Genética a la Enfermedad / Hipertensión Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos