Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Division of Psychological and Social Medicine and Developmental Neurosciences
- University Medicine (Faculty of Medicine and University Hospital)
- Faculty of Psychology
- Karolinska Institutet
- University College London
- Imperial College London
- University of Copenhagen
- University of North Carolina at Chapel Hill
- Curtin University
- University of Western Australia
- Utrecht University
- Altrecht Mental Health Institute
- University of Gothenburg
- University of Oslo
- BioRealm LLC
- Oregon Research Institute
- University of Pennsylvania
- Stockholm City Council
- University of Otago
- Wellcome Sanger Institute
- University of Split
- The Center for Eating Disorders
- South London and Maudsley NHS Foundation Trust
- RWTH Aachen University
- Klinikum Frankfurt (Oder)
- University of Padua
- University of Basel
- University of Michigan, Ann Arbor
- University of Montpellier
- University of Minnesota System
- University of Bristol
- Hannover Medical School (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 - Center for Biomedical Research Network
- Stanford University
- University of Würzburg
- Estonian Biocentre
- Massachusetts Institute of Technology (MIT)
- Department of Child and Adolescent Psychiatry and Psychotherapy
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
Original language | English |
---|---|
Pages (from-to) | 482-493 |
Number of pages | 12 |
Journal | Nature genetics |
Volume | 52 |
Issue number | 5 |
Publication status | Published - 1 May 2020 |
Peer-reviewed | Yes |
External IDs
PubMed | 32341526 |
---|---|
ORCID | /0000-0003-2132-4445/work/149437503 |