Analysis of shared heritability in common disorders of the brain

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Massachusetts General Hospital
  • Broad Institute of Harvard University and MIT
  • Massachusetts Institute of Technology (MIT)
  • Harvard University
  • University College London
  • Stanford University
  • Cardiff University
  • Ludwig-Maximilians-Universität München (LMU)
  • Charité – Universitätsmedizin Berlin
  • New Jersey Institute of Technology
  • INSERM - Institut national de la santé et de la recherche médicale
  • Institut Pasteur de Lille
  • Université de Lille
  • RIKEN Center for Integrative Medical Sciences
  • Kyoto University
  • INSERM U1061 - Neuropsychiatry: Epidemiological and Clinical Research
  • Université de Montpellier
  • CHU Montpellier
  • UMR 1219
  • Université de Bordeaux
  • CHU Hôpitaux de Rouen
  • Inserm U1245
  • Commissariat à l’énergie atomique et aux énergies alternatives (CEA)
  • Assistance publique – Hôpitaux de Paris
  • 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
  • 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

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

OriginalspracheEnglisch
Aufsatznummer8757
Seiten (von - bis)1-12
Seitenumfang13
FachzeitschriftScience
Jahrgang360
Ausgabenummer6395
PublikationsstatusElektronische Veröffentlichung vor Drucklegung - 24 Apr. 2018
Peer-Review-StatusJa

Externe IDs

PubMed 29930110
ORCID /0000-0003-2132-4445/work/160950891
ORCID /0000-0002-2666-859X/work/160952945

Schlagworte

ASJC Scopus Sachgebiete