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Analysis of shared heritability in common disorders of the brain.
Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K; Walters, Raymond K; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N; Reitz, Christiane; Goate, Alison M; Huentelman, Matthew J; Kamboh, M Ilyas; Larson, Eric B; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A; Farrer, Lindsay A; Barnes, Lisa L; Beach, Thomas G; Demirci, F Yesim; Head, Elizabeth; Hulette, Christine M; Jicha, Gregory A; Kauwe, John S K; Kaye, Jeffrey A; Leverenz, James B; Levey, Allan I; Lieberman, Andrew P; Pankratz, Vernon S; Poon, Wayne W.
Afiliación
  • Anttila V; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA. verneri.anttila@gmail.com acorvin@tcd.ie bneale@broadinstitute.org.
  • Bulik-Sullivan B; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Finucane HK; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Walters RK; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Bras J; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Duncan L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Escott-Price V; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Falcone GJ; Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Gormley P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Malik R; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Patsopoulos NA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Ripke S; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Wei Z; UK Dementia Research Institute, University College London, London, UK.
  • Yu D; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
  • Lee PH; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Turley P; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Grenier-Boley B; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Chouraki V; Department of Psychiatry and Behavioral Science, Stanford University, Stanford, California, USA.
  • Kamatani Y; Cardiff University, Medical Research Council Center for Neuropsychiatric Genetics & Genomics, Institute of Psychology, Medicine & Clinical Neuroscience, Cardiff, UK.
  • Berr C; Dementia Research Institute, Cardiff University, Cardiff, UK.
  • Letenneur L; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Hannequin D; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Amouyel P; Harvard Medical School, Boston, MA, USA.
  • Boland A; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Deleuze JF; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Duron E; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Vardarajan BN; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Reitz C; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
  • Goate AM; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Huentelman MJ; Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kamboh MI; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Larson EB; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Rogaeva E; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • St George-Hyslop P; Charite Universitatsmedizin Berlin, Berlin, Germany.
  • Hakonarson H; Department of Computer Science, New Jersey Institute of Technology, New Jersey, USA.
  • Kukull WA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Farrer LA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Barnes LL; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Beach TG; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Demirci FY; Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
  • Head E; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Hulette CM; INSERM U1167 LabEx DISTALZ, Lille, France.
  • Jicha GA; Institut Pasteur de Lille, U1167, Lille, France.
  • Kauwe JSK; Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
  • Kaye JA; INSERM U1167 LabEx DISTALZ, Lille, France.
  • Leverenz JB; Institut Pasteur de Lille, U1167, Lille, France.
  • Levey AI; Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
  • Lieberman AP; Centre Hosp. Univ Lille, Lille, France.
  • Pankratz VS; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Poon WW; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Science ; 360(6395)2018 06 22.
Article en En | MEDLINE | ID: mdl-29930110
ABSTRACT
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalopatías / Trastornos Mentales Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Science Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalopatías / Trastornos Mentales Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Science Año: 2018 Tipo del documento: Article