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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Nature Genetics |
Vol/bind | 52 |
Sider (fra-til) | 482-493 |
ISSN | 1061-4036 |
DOI | |
Status | Udgivet - maj 2020 |
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. / Bryois, Julien; Skene, Nathan G.; Hansen, Thomas Folkmann; Kogelman, Lisette J.A.; Watson, Hunna J.; Liu, Zijing; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Adan, Roger; Alfredsson, Lars; Ando, Tetsuya; Andreassen, Ole; Baker, Jessica; Bergen, Andrew; Berrettini, Wade; Birgegård, Andreas; Boden, Joseph; Boehm, Ilka; Boni, Claudette; Boraska Perica, Vesna; Brandt, Harry; Breen, Gerome; Bryois, Julien; Buehren, Katharina; Bulik, Cynthia; Burghardt, Roland; Cassina, Matteo; Cichon, Sven; Clementi, Maurizio; Coleman, Jonathan; Cone, Roger; Courtet, Philippe; Crawford, Steven; Crow, Scott; Crowley, James; Danner, Unna; Davis, Oliver; de Zwaan, Martina; Dedoussis, George; Degortes, Daniela; DeSocio, Janiece; Dick, Danielle; Hinney, Anke; Grove, Jakob; Larsen, Janne; Mattheisen, Manuel; Mortensen, Preben Bo; Petersen, Liselotte; Werge, Thomas; Zeggini, Eleftheria; Zerwas, Stephanie; Zipfel, Stephan ; International Headache Genetics Consortium; Anttila, Verneri; Artto, Ville; Belin, Andrea Carmine; Christensen, Anne Francke; Esserlind, Ann-Louise; Kogelman, Lisette J.A.; Olesen, Jes; Olesen, Jes; Winsvold, Bendik S; Zhao, Huiying; Zwart, John-Anker; 23andMe Research Team.
I: Nature Genetics, Bind 52, 05.2020, s. 482-493.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
AU - Bryois, Julien
AU - Skene, Nathan G.
AU - Hansen, Thomas Folkmann
AU - Kogelman, Lisette J.A.
AU - Watson, Hunna J.
AU - Liu, Zijing
AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium
AU - Adan, Roger
AU - Alfredsson, Lars
AU - Ando, Tetsuya
AU - Andreassen, Ole
AU - Baker, Jessica
AU - Bergen, Andrew
AU - Berrettini, Wade
AU - Birgegård, Andreas
AU - Boden, Joseph
AU - Boehm, Ilka
AU - Boni, Claudette
AU - Boraska Perica, Vesna
AU - Brandt, Harry
AU - Breen, Gerome
AU - Bryois, Julien
AU - Buehren, Katharina
AU - Bulik, Cynthia
AU - Burghardt, Roland
AU - Cassina, Matteo
AU - Cichon, Sven
AU - Clementi, Maurizio
AU - Coleman, Jonathan
AU - Cone, Roger
AU - Courtet, Philippe
AU - Crawford, Steven
AU - Crow, Scott
AU - Crowley, James
AU - Danner, Unna
AU - Davis, Oliver
AU - de Zwaan, Martina
AU - Dedoussis, George
AU - Degortes, Daniela
AU - DeSocio, Janiece
AU - Dick, Danielle
AU - Hinney, Anke
AU - Grove, Jakob
AU - Larsen, Janne
AU - Mattheisen, Manuel
AU - Mortensen, Preben Bo
AU - Petersen, Liselotte
AU - Werge, Thomas
AU - Zeggini, Eleftheria
AU - Zerwas, Stephanie
AU - Zipfel, Stephan
AU - International Headache Genetics Consortium
AU - Anttila, Verneri
AU - Artto, Ville
AU - Belin, Andrea Carmine
AU - Christensen, Anne Francke
AU - Esserlind, Ann-Louise
AU - Kogelman, Lisette J.A.
AU - Olesen, Jes
AU - Olesen, Jes
AU - Winsvold, Bendik S
AU - Zhao, Huiying
AU - Zwart, John-Anker
AU - 23andMe Research Team
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-020-0610-9
DO - 10.1038/s41588-020-0610-9
M3 - Journal article
C2 - 32341526
AN - SCOPUS:85084195663
VL - 52
SP - 482
EP - 493
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -