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

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 syste...

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Detalles Bibliográficos
Autores: Bryois, Juliene, Skene, Nathan G., Folkmann Hansen, Thomas, Kogelman, Lisette J. A., Watson, Hunna J., Liu, Zijing, Eating Disorders Working Group of the Psychiatric Genomics Consortium, International Headache Genetics Consortium, 23andMe Research Team, Brueggeman, Leo, Breen, Gerome, Bulik, Cynthia M., Arenas, Ernest, Hjerling-Leffler, Jens, Sullivan, Patrick F.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182511
Acceso en línea:https://hdl.handle.net/2445/182511
Access Level:acceso abierto
Palabra clave:Gens
Cervell
Malaltia de Parkinson
Genes
Brain
Parkinson's disease
Descripción
Sumario: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.

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