Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Eating Disorders Working Group of the Psychiatric Genomics Consortium - (Autor:in)
  • International Headache Genetics Consortium - (Autor:in)
  • 23andMe Research Team - (Autor:in)
  • Psychosoziale Medizin und Entwicklungsneurowissenschaften
  • Hochschulmedizin (Medizinische Fakultät und Universitätsklinikum)
  • Fakultät Psychologie
  • Karolinska Institutet
  • University College London
  • Imperial College London
  • Universität Kopenhagen
  • University of North Carolina at Chapel Hill
  • Curtin University
  • University of Western Australia
  • Utrecht University
  • Altrecht Mental Health Institute
  • University of Gothenburg
  • National Center of Neurology and Psychiatry Kodaira
  • University of Oslo
  • BioRealm LLC
  • Oregon Research Institute
  • University of Pennsylvania
  • Stockholm City Council
  • University of Otago
  • INSERM - Institut national de la santé et de la recherche médicale
  • Wellcome Sanger Institute
  • University of Split
  • The Center for Eating Disorders
  • Medical Research Council (MRC)
  • South London and Maudsley NHS Foundation Trust
  • RWTH Aachen University
  • Klinikum Frankfurt (Oder)
  • Università degli studi di Padova
  • Universität Basel
  • University of Michigan, Ann Arbor
  • Université de Montpellier
  • University of Minnesota System
  • University of Bristol
  • Medizinische Hochschule Hannover (MHH)
  • Harokopio University
  • Seattle University
  • Virginia Commonwealth University
  • National and Kapodistrian University of Athens
  • Université de Nantes
  • University of Medical Sciences Poznan
  • Barcelona Institute of Science and Technology (BIST)
  • Pompeu Fabra University
  • CIBER - Centro de Investigación Biomédica en Red
  • Stanford University
  • Julius-Maximilians-Universität Würzburg
  • Estonian Biocentre
  • Massachusetts Institute of Technology (MIT)
  • Klinik und Poliklinik für Kinder- und Jugendmedizin

Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease.

Details

OriginalspracheEnglisch
Seiten (von - bis)482-493
Seitenumfang12
FachzeitschriftNature genetics
Jahrgang52
Ausgabenummer5
PublikationsstatusVeröffentlicht - 1 Mai 2020
Peer-Review-StatusJa

Externe IDs

PubMed 32341526
ORCID /0000-0003-2132-4445/work/149437503

Schlagworte

ASJC Scopus Sachgebiete