Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease
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Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2020-05-01
Date Acceptance
2020-03-06
Citation
Nature Genetics, 2020, 52 (5), pp.482-493
ISSN
1061-4036
Publisher
Nature Research
Start Page
482
End Page
493
Journal / Book Title
Nature Genetics
Volume
52
Issue
5
Copyright Statement
© 2020 Springer Nature Limited.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32341526
PII: 10.1038/s41588-020-0610-9
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
ENTERIC NERVOUS-SYSTEM
RISK LOCI
METAANALYSIS
NUCLEUS
ALZHEIMERS
IMMUNITY
TISSUES
NEURONS
HERITABILITY
Animals
Brain
Genome-Wide Association Study
Humans
Mice
Neurons
Parkinson Disease
Transcriptome
Eating Disorders Working Group of the Psychiatric Genomics Consortium
International Headache Genetics Consortium
23andMe Research Team
Brain
Neurons
Animals
Humans
Mice
Parkinson Disease
Genome-Wide Association Study
Transcriptome
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-04-27