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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
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- Bryois, J. (author)
- Karolinska Institutet
- Skene, N. G. (author)
- Hansen, T. F. (author)
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- Kogelman, L. J. A. (author)
- Watson, H. J. (author)
- Liu, Z. (author)
- Alfredsson, L. (author)
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- Baker, J. (author)
- Bergen, A. (author)
- Berrettini, W. (author)
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- Farmer, A. (author)
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- Fernández-Aranda, F. (author)
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- Fischer, K. (author)
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- Foretova, L. (author)
- Forstner, A. (author)
- Forzan, M. (author)
- Franklin, C. (author)
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- Montgomery, G. (author)
- Mortensen, P. B. (author)
- Munn-Chernoff, M. (author)
- Nacmias, B. (author)
- Navratilova, M. (author)
- Norring, C. (author)
- Ntalla, I. (author)
- Olsen, C. (author)
- Ophoff, R. (author)
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- Padyukov, L. (author)
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- van Furth, E. (author)
- Wade, T. (author)
- Wagner, G. (author)
- Walton, E. (author)
- Watson, H. (author)
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- Widen, E. (author)
- Woodside, D. B. (author)
- Yao, S. (author)
- Yilmaz, Z. (author)
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- Zerwas, S. (author)
- Zipfel, S. (author)
- Anttila, V. (author)
- Artto, V. (author)
- Belin, A. C. (author)
- de Boer, I. (author)
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- Børte, S. (author)
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- Cherkas, L. (author)
- Christensen, A. F. (author)
- Cormand, B. (author)
- Cuenca-Leon, E. (author)
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- van Duijn, C. (author)
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- Esserlind, A. L. (author)
- Ferrari, M. (author)
- Frants, R. R. (author)
- Freilinger, T. (author)
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- Gormley, P. (author)
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- Hamalainen, E. (author)
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- Zhao, H. (author)
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- Agee, M. (author)
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- Auton, A. (author)
- Bell, R. (author)
- Bryc, K. (author)
- Elson, S. (author)
- Fontanillas, P. (author)
- Furlotte, N. (author)
- Heilbron, K. (author)
- Hinds, D. (author)
- Huber, K. (author)
- Kleinman, A. (author)
- Litterman, N. (author)
- McCreight, J. (author)
- McIntyre, M. (author)
- Mountain, J. (author)
- Noblin, E. (author)
- Northover, C. (author)
- Pitts, S. (author)
- Sathirapongsasuti, J. (author)
- Sazonova, O. (author)
- Shelton, J. (author)
- Shringarpure, S. (author)
- Tian, C. (author)
- Tung, J. (author)
- Vacic, V. (author)
- Wilson, C. (author)
- Brueggeman, L. (author)
- Breen, G. (author)
- Bulik, C. M. (author)
- Arenas, E. (author)
- Hjerling-Leffler, J. (author)
- Sullivan, P. F. (author)
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- (creator_code:org_t)
- 2020-04-27
- 2020
- English.
- In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- hemoglobin A1c
- RNA
- Article
- autism
- bipolar disorder
- body mass
- cells by body anatomy
- cerebrovascular accident
- cholinergic nerve cell
- coronary artery disease
- disease exacerbation
- educational status
- gene expression
- genetic association
- genetic correlation
- genetic identification
- genome-wide association study
- glycemic control
- human
- human tissue
- inflammatory bowel disease
- mental disease
- monoamine nerve cell
- neurologic disease
- neurosis
- non insulin dependent diabetes mellitus
- nonhuman
- oligodendroglia
- Parkinson disease
- parkinsonism
- priority journal
- RNA sequencing
- schizophrenia
- single cell RNA seq
- transcriptomics
- upregulation
- waist hip ratio
Publication and Content Type
- ref (subject category)
- art (subject category)
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