Analysis of shared heritability in common disorders of the brain

Research output: Contribution to journalArticle

Authors

  • Brainstorm Consortium

Colleges, School and Institutes

External organisations

  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
  • Department of Psychiatry and Behavioral Science, Stanford University, Stanford, California, USA.
  • Cardiff University
  • Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Environmental Health, Harvard T H Chan School of Public Health, Boston, MA, USA.
  • Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
  • Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Charite Universitatsmedizin Berlin, Berlin, Germany.
  • Department of Computer Science, New Jersey Institute of Technology, New Jersey, USA.
  • Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
  • Centre Hosp. Univ Lille, Lille, France.
  • Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital Gui de Chauliac, Montpellier, France.
  • Composantes Innées de la Response Immunitaire et Différenciation, University of Bordeaux, Bordeaux, France.
  • Inserm U1245, Rouen, France.
  • Centre National de Recherche en Génomique Humaine (CNRGH), Institut de biologie François Jacob, CEA, Evry, France.
  • Hôpital Paul Brousse Université Paris Sud XI, Le Kremlin-Bicêtre, Paris, France.
  • Gertrude H. Sergievsky Center and Dept of Neurology, Columbia University, New York, NY, USA.
  • Columbia University, New York, New York 10027, USA
  • Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Translational Genomics Research Institute, Neurogenomics Division, Phoenix, AZ, USA.
  • Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 1] Department of Medicine, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  • Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
  • University of Cambridge
  • Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • National Alzheimer Coordinating Center (NACC), Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
  • Department of Behavioral Sciences, Rush Medical College, Chicago, IL, USA.
  • Banner Sun Health Research Institute, Sun City, AZ, USA.
  • Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
  • Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
  • College of Medicine, University of Kentucky, Lexington, KY, USA.
  • Department of Biology, Brigham Young University, Provo, UT, USA.
  • Layton Aging & Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR, USA.
  • Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  • Institute of Applied Health Research, University of Birmingham, Birmingham, Uk.
  • Analytic Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA.

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.

Details

Original languageEnglish
Article numbereaap8757
Number of pages13
JournalScience
Volume360
Issue number6395
Publication statusPublished - 22 Jun 2018