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Analysis of shared heritability in common disorders of the brain

  • The Brainstorm Consortium
  • Massachusetts General Hospital
  • Broad Institute
  • Massachusetts Institute of Technology
  • Harvard University
  • University College London
  • Stanford University
  • Cardiff University
  • Ludwig Maximilian University of Munich
  • Charité – Universitätsmedizin Berlin
  • New Jersey Institute of Technology
  • Institut national de la santé et de la recherche médicale
  • Institut Pasteur de Lille
  • Université de Lille
  • RIKEN
  • Kyoto University
  • INSERM U1061 - Neuropsychiatry: Epidemiological and Clinical Research
  • Université de Montpellier
  • CHU Montpellier
  • Université de Bordeaux
  • CHU Hôpitaux de Rouen
  • Inserm U1245
  • Commissariat à l’énergie atomique et aux énergies alternatives
  • Hôpital Broca
  • Université Paris-Saclay
  • Columbia University
  • Icahn School of Medicine at Mount Sinai
  • Translational Genomics Research Institute
  • University of Pittsburgh
  • Kaiser Permanente
  • University of Washington
  • University of Toronto
  • University of Cambridge
  • Division of Neurology
  • University of Pennsylvania
  • Boston University
  • Rush University
  • Banner Health
  • University of Kentucky
  • Duke University
  • Brigham Young University
  • Oregon Health and Science University
  • Cleveland Clinic Foundation
  • Emory University
  • University of Michigan, Ann Arbor
  • University of New Mexico

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number8757
JournalScience
Volume360
Issue number6395
DOIs
Publication statusPublished - 22 Jun 2018

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