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

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 Boni; Vesna Boraska Perica; Harry Brandt; Gerome Breen; 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; Xavier Estivill; Anne Farmer; Angela Favaro; Fernando Fernández-Aranda; Manfred Fichter; Krista Fischer; Manuel Föcker; Lenka Foretova; Andreas Forstner; Monica Forzan; Christopher Franklin; Steven Gallinger; Héléna Gaspar; Ina Giegling; Johanna Giuranna; Paola Giusti-Rodríquez; Fragiskos Gonidakis; Scott Gordon; Philip Gorwood; Monica Gratacos Mayora; Jakob Grove; Sébastien Guillaume; Yiran Guo; Hakon Hakonarson; Katherine Halmi; Ken Hanscombe; Konstantinos Hatzikotoulas; Joanna Hauser; Johannes Hebebrand; Sietske Helder; Anjali Henders; Stefan Herms; Beate Herpertz-Dahlmann; Wolfgang Herzog; Anke Hinney; L. John Horwood; Christopher Hübel; Laura Huckins; James Hudson; Hartmut Imgart; Hidetoshi Inoko; Vladimir Janout; Susana Jiménez-Murcia; Craig Johnson; Jennifer Jordan; Antonio Julià; Anders Juréus; Gursharan Kalsi; Deborah Kaminská; Allan Kaplan; Jaakko Kaprio; Leila Karhunen; Andreas Karwautz; Martien Kas; Walter Kaye; James Kennedy; Martin Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl Ri Kim; Katherine Kirk; Lars Klareskog; Kelly Klump; Gun Peggy Knudsen; Maria La Via; Mikael Landén; Janne Larsen; Stephanie Le Hellard; Virpi Leppä; Robert Levitan; Dong Li; Paul Lichtenstein; Lisa Lilenfeld; Bochao Danae Lin; Jolanta Lissowska; Jurjen Luykx; Pierre J Magistretti; Mario Maj; Katrin Mannik; Sara Marsal; Christian Marshall; Nicholas Martin; Manuel Mattheisen; Morten Mattingsdal; Sara McDevitt; Peter McGuffin; Sarah Medland; Andres Metspalu; Ingrid Meulenbelt; Nadia Micali; James Mitchell; Karen Mitchell; Palmiero Monteleone; Alessio Maria Monteleone; Grant Montgomery; Preben Bo Mortensen; Melissa Munn-Chernoff; Benedetta Nacmias; Marie Navratilova; Claes Norring; Ioanna Ntalla; Catherine Olsen; Roel Ophoff; Julie O’Toole; Leonid Padyukov; Aarno Palotie; Jacques Pantel; Hana Papezova; Richard Parker; John Pearson; Nancy Pedersen; Liselotte Petersen; Dalila Pinto; Kirstin Purves; Raquel Rabionet; Anu Raevuori; Nicolas Ramoz; Ted Reichborn-Kjennerud; Valdo Ricca; Samuli Ripatti; Stephan Ripke; Franziska Ritschel; Marion Roberts; Alessandro Rotondo; Dan Rujescu; Filip Rybakowski; Paolo Santonastaso; André Scherag; Stephen Scherer; Ulrike Schmidt; Nicholas Schork; Alexandra Schosser; Jochen Seitz; Lenka Slachtova; P. Eline Slagboom; Margarita Slof-Op ‘t Landt; Agnieszka Slopien; Sandro Sorbi; Michael Strober; Garret Stuber; Patrick Sullivan; Beata Świątkowska; Jin Szatkiewicz; Ioanna Tachmazidou; Elena Tenconi; Laura Thornton; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Artemis Tsitsika; Marta Tyszkiewicz-Nwafor; Konstantinos Tziouvas; Annemarie van Elburg; Eric van Furth; Tracey Wade; Gudrun Wagner; Esther Walton; Hunna Watson; Thomas Werge; David Whiteman; Elisabeth Widen; D. Blake Woodside; Shuyang Yao; Zeynep Yilmaz; Eleftheria Zeggini; Stephanie Zerwas; Stephan Zipfel; Verneri Anttila; Ville Artto; Andrea Carmine Belin; Irene de Boer; Dorret I Boomsma; Sigrid Børte; Daniel I Chasman; Lynn Cherkas; Anne Francke Christensen; Bru Cormand; Ester Cuenca-Leon; George Davey-Smith; Martin Dichgans; Cornelia van Duijn; Tonu Esko; Ann Louise Esserlind; Michel Ferrari; Rune R Frants; Tobias Freilinger; Nick Furlotte; Padhraig Gormley; Lyn Griffiths; Eija Hamalainen; Marjo Hiekkala; M. Arfan Ikram; Andres Ingason; Marjo Riitta Järvelin; Risto Kajanne; Mikko Kallela; Mari Kaunisto; Christian Kubisch; Mitja Kurki; Tobias Kurth; Lenore Launer; Terho Lehtimaki; Davor Lessel; Lannie Ligthart; Nadia Litterman; Arn van den Maagdenberg; Alfons Macaya; Rainer Malik; Massimo Mangino; George McMahon; Bertram Muller-Myhsok; Benjamin M Neale; Carrie Northover; Dale R Nyholt; Jes Olesen; Priit Palta; Linda Pedersen; Danielle Posthuma; Patricia Pozo-Rosich; Alice Pressman; Olli Raitakari; Markus Schürks; Celia Sintas; Kari Stefansson; Hreinn Stefansson; Stacy Steinberg; David Strachan; Gisela Terwindt; Marta Vila-Pueyo; Maija Wessman; Bendik S Winsvold; Huiying Zhao; John Anker Zwart; Michelle Agee; Babak Alipanahi; Adam Auton; Robert Bell; Katarzyna Bryc; Sarah Elson; Pierre Fontanillas; Nicholas Furlotte; Karl Heilbron; David Hinds; Karen Huber; Aaron Kleinman; Jennifer McCreight; Matthew McIntyre; Joanna Mountain; Elizabeth Noblin; Steven Pitts; J Sathirapongsasuti; Olga Sazonova; Janie Shelton; Suyash Shringarpure; Chao Tian; Joyce Tung; Vladimir Vacic; Catherine Wilson; Leo Brueggeman; Cynthia M Bulik; Ernest Arenas; Jens Hjerling-Leffler; Patrick F Sullivan

doi:10.1038/s41588-020-0610-9

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

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, …

06/03/2020

DOI: https://doi.org/10.1038/s41588-020-0610-9

Résumé

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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Titre: Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
Créateurs - sans rôle: 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 Boni
Vesna Boraska Perica
Harry Brandt
Gerome Breen
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
Xavier Estivill
Anne Farmer
Angela Favaro
Fernando Fernández-Aranda
Manfred Fichter
Krista Fischer
Manuel Föcker
Lenka Foretova
Andreas Forstner
Monica Forzan
Christopher Franklin
Steven Gallinger
Héléna Gaspar
Ina Giegling
Johanna Giuranna
Paola Giusti-Rodríquez
Fragiskos Gonidakis
Scott Gordon
Philip Gorwood
Monica Gratacos Mayora
Jakob Grove
Sébastien Guillaume
Yiran Guo
Hakon Hakonarson
Katherine Halmi
Ken Hanscombe
Konstantinos Hatzikotoulas
Joanna Hauser
Johannes Hebebrand
Sietske Helder
Anjali Henders
Stefan Herms
Beate Herpertz-Dahlmann
Wolfgang Herzog
Anke Hinney
L. John Horwood
Christopher Hübel
Laura Huckins
James Hudson
Hartmut Imgart
Hidetoshi Inoko
Vladimir Janout
Susana Jiménez-Murcia
Craig Johnson
Jennifer Jordan
Antonio Julià
Anders Juréus
Gursharan Kalsi
Deborah Kaminská
Allan Kaplan
Jaakko Kaprio
Leila Karhunen
Andreas Karwautz
Martien Kas
Walter Kaye
James Kennedy
Martin Kennedy
Anna Keski-Rahkonen
Kirsty Kiezebrink
Youl Ri Kim
Katherine Kirk
Lars Klareskog
Kelly Klump
Gun Peggy Knudsen
Maria La Via
Mikael Landén
Janne Larsen
Stephanie Le Hellard
Virpi Leppä
Robert Levitan
Dong Li
Paul Lichtenstein
Lisa Lilenfeld
Bochao Danae Lin
Jolanta Lissowska
Jurjen Luykx
Pierre J Magistretti
Mario Maj
Katrin Mannik
Sara Marsal
Christian Marshall
Nicholas Martin
Manuel Mattheisen
Morten Mattingsdal
Sara McDevitt
Peter McGuffin
Sarah Medland
Andres Metspalu
Ingrid Meulenbelt
Nadia Micali
James Mitchell
Karen Mitchell
Palmiero Monteleone
Alessio Maria Monteleone
Grant Montgomery
Preben Bo Mortensen
Melissa Munn-Chernoff
Benedetta Nacmias
Marie Navratilova
Claes Norring
Ioanna Ntalla
Catherine Olsen
Roel Ophoff
Julie O’Toole
Leonid Padyukov
Aarno Palotie
Jacques Pantel
Hana Papezova
Richard Parker
John Pearson
Nancy Pedersen
Liselotte Petersen
Dalila Pinto
Kirstin Purves
Raquel Rabionet
Anu Raevuori
Nicolas Ramoz
Ted Reichborn-Kjennerud
Valdo Ricca
Samuli Ripatti
Stephan Ripke
Franziska Ritschel
Marion Roberts
Alessandro Rotondo
Dan Rujescu
Filip Rybakowski
Paolo Santonastaso
André Scherag
Stephen Scherer
Ulrike Schmidt
Nicholas Schork
Alexandra Schosser
Jochen Seitz
Lenka Slachtova
P. Eline Slagboom
Margarita Slof-Op ‘t Landt
Agnieszka Slopien
Sandro Sorbi
Michael Strober
Garret Stuber
Patrick Sullivan
Beata Świątkowska
Jin Szatkiewicz
Ioanna Tachmazidou
Elena Tenconi
Laura Thornton
Alfonso Tortorella
Federica Tozzi
Janet Treasure
Artemis Tsitsika
Marta Tyszkiewicz-Nwafor
Konstantinos Tziouvas
Annemarie van Elburg
Eric van Furth
Tracey Wade
Gudrun Wagner
Esther Walton
Hunna Watson
Thomas Werge
David Whiteman
Elisabeth Widen
D. Blake Woodside
Shuyang Yao
Zeynep Yilmaz
Eleftheria Zeggini
Stephanie Zerwas
Stephan Zipfel
Verneri Anttila
Ville Artto
Andrea Carmine Belin
Irene de Boer
Dorret I Boomsma
Sigrid Børte
Daniel I Chasman
Lynn Cherkas
Anne Francke Christensen
Bru Cormand
Ester Cuenca-Leon
George Davey-Smith
Martin Dichgans
Cornelia van Duijn
Tonu Esko
Ann Louise Esserlind
Michel Ferrari
Rune R Frants
Tobias Freilinger
Nick Furlotte
Padhraig Gormley
Lyn Griffiths
Eija Hamalainen
Marjo Hiekkala
M. Arfan Ikram
Andres Ingason
Marjo Riitta Järvelin
Risto Kajanne
Mikko Kallela
Mari Kaunisto
Christian Kubisch
Mitja Kurki
Tobias Kurth
Lenore Launer
Terho Lehtimaki
Davor Lessel
Lannie Ligthart
Nadia Litterman
Arn van den Maagdenberg
Alfons Macaya
Rainer Malik
Massimo Mangino
George McMahon
Bertram Muller-Myhsok
Benjamin M Neale
Carrie Northover
Dale R Nyholt
Jes Olesen
Priit Palta
Linda Pedersen
Danielle Posthuma
Patricia Pozo-Rosich
Alice Pressman
Olli Raitakari
Markus Schürks
Celia Sintas
Kari Stefansson
Hreinn Stefansson
Stacy Steinberg
David Strachan
Gisela Terwindt
Marta Vila-Pueyo
Maija Wessman
Bendik S Winsvold
Huiying Zhao
John Anker Zwart
Michelle Agee
Babak Alipanahi
Adam Auton
Robert Bell
Katarzyna Bryc
Sarah Elson
Pierre Fontanillas
Nicholas Furlotte
Karl Heilbron
David Hinds
Karen Huber
Aaron Kleinman
Jennifer McCreight
Matthew McIntyre
Joanna Mountain
Elizabeth Noblin
Steven Pitts
J Sathirapongsasuti
Olga Sazonova
Janie Shelton
Suyash Shringarpure
Chao Tian
Joyce Tung
Vladimir Vacic
Catherine Wilson
Leo Brueggeman
Cynthia M Bulik
Ernest Arenas
Jens Hjerling-Leffler
Patrick F Sullivan
Éditeur: Springer Nature
Identifiants: 99139569109311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English
Type de ressource: Journal article