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

Eating Disorders Working Group of the Psychiatric Genomics Consortium, International Headache Genetics Consortium, 23andMe Research Team, Julien Bryois, Nathan G. Skene, Thomas Folkmann Hansen, Lisette J.A. Kogelman, Hunna J. Watson, Zijing Liu, Roger Adan, Lars Alfredsson, Tetsuya Ando, Ole Andreassen, Jessica Baker, Andrew Bergen, Wade Berrettini, Andreas Birgegård, Joseph Boden, Ilka Boehm, Claudette BoniVesna Boraska Perica, Harry Brandt, Gerome Breen, Julien Bryois, Katharina Buehren, Cynthia Bulik, Roland Burghardt, Matteo Cassina, Sven Cichon, Maurizio Clementi, Jonathan Coleman, Roger Cone, Philippe Courtet, Steven Crawford, Scott Crow, James Crowley, Unna Danner, Oliver Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece DeSocio, Danielle Dick, Dimitris Dikeos, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie Duncan, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Sandro Sorbi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalNature Genetics
DOIs
Publication statusAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Genetics

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