Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Lynne Krohn; Karl Heilbron; Cornelis Blauwendraat; Regina H Reynolds; Eric Yu; Konstantin Senkevich; Uladzislau Rudakou; Mehrdad A Estiar; Emil K Gustavsson; Kajsa Brolin; Jennifer A Ruskey; Kathryn Freeman; Farnaz Asayesh; Ruth Chia; Isabelle Arnulf; Michele T M Hu; Jacques Y Montplaisir; Jean-François Gagnon; Alex Desautels; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Andrea Bernardini; Birgit Högl; Ambra Stefani; Abubaker Ibrahim; Karel Šonka; David Kemlink; Wolfgang Oertel; Annette Janzen; Giuseppe Plazzi; Francesco Biscarini; Elena Antelmi; Michela Figorilli; Monica Puligheddu; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Döring; Christelle Charley Monaca; Anna Heidbreder; Luigi Ferini-Strambi; Femke Dijkstra; Mineke Viaene; Beatriz Abril; Bradley F Boeve; Sonja W Scholz; Mina Ryten; Sara Bandres-Ciga; Alastair Noyce; Paul Cannon; Lasse Pihlstrøm; Mike A Nalls; Andrew B Singleton; Guy A Rouleau; Ronald B Postuma; Ziv Gan-Or; Yves Dauvilliers; Valérie Cochen de Cock; Stella Aslibekyan; Adam Auton; Elizabeth Babalola; Robert K Bell; Jessica Bielenberg; Katarzyna Bryc; Emily Bullis; Daniella Coker; Gabriel Cuellar Partida; Devika Dhamija; Sayantan Das; Sarah L Elson; Teresa Filshtein; Kipper Fletez-Brant; Pierre Fontanillas; Will Freyman; Pooja M Gandhi; Barry Hicks; David A Hinds; Ethan M Jewett; Yunxuan Jiang; Katelyn Kukar; Keng-Han Lin; Maya Lowe; Jey C Mccreight; Matthew H Mcintyre; Steven J Micheletti; Meghan E Moreno; Joanna L Mountain; Priyanka Nandakumar; Elizabeth S Noblin; Jared O'Connell; Aaron A Petrakovitz; G David Poznik; Morgan Schumacher; Anjali J Shastri; Janie F Shelton; Jingchunzi Shi; Suyash Shringarpure; Vinh Tran; Joyce Y Tung; Xin Wang; Wei Wang; Catherine H Weldon; Peter Wilton; Alejandro Hernandez; Corinna Wong; Christophe Toukam Tchakouté

doi:10.1038/s41467-022-34732-5

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Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Journal article

Open access

Peer reviewed

Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Lynne Krohn, Karl Heilbron, Cornelis Blauwendraat, Regina H Reynolds, Eric Yu, Konstantin Senkevich, Uladzislau Rudakou, Mehrdad A Estiar, Emil K Gustavsson, Kajsa Brolin, …

Nature Communications, Vol.13(1)

05/12/2022

DOI: https://doi.org/10.1038/s41467-022-34732-5

Abstract

Brain

Genome-Wide Association Study

Humans

Parkinson Disease / genetics

REM Sleep Behavior Disorder / genetics

Synucleinopathies

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2 . Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.

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Title: Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
Creators - without role: Lynne Krohn - McGill University
Karl Heilbron - 23andMe
Cornelis Blauwendraat - National Institute on Aging
Regina H Reynolds - University College London
Eric Yu - McGill University
Konstantin Senkevich - McGill University
Uladzislau Rudakou - McGill University
Mehrdad A Estiar - McGill University
Emil K Gustavsson - Great Ormond Street Hospital
Kajsa Brolin - Lund University
Jennifer A Ruskey - Montreal Neurological Institute and Hospital
Kathryn Freeman - Montreal Neurological Institute and Hospital
Farnaz Asayesh - McGill University
Ruth Chia - National Institute on Aging
Isabelle Arnulf - Sorbonne Université
Michele T M Hu - 23andMe
Jacques Y Montplaisir - Hôpital du Sacré-Cœur de Montréal
Jean-François Gagnon - Université du Québec à Montréal
Alex Desautels - Hôpital du Sacré-Cœur de Montréal
Gian Luigi Gigli - University of Udine
Mariarosaria Valente - University of Udine
Francesco Janes - University of Udine
Andrea Bernardini - University of Udine
Birgit Högl - Innsbruck Medical University
Ambra Stefani - Innsbruck Medical University
Abubaker Ibrahim - Universität Innsbruck
Karel Šonka - Charles University
David Kemlink - Charles University
Wolfgang Oertel - Philipps University of Marburg
Annette Janzen - Philipps University of Marburg
Giuseppe Plazzi - University of Modena and Reggio Emilia
Francesco Biscarini - University of Bologna
Elena Antelmi - Institute of Neurological Sciences
Michela Figorilli - University of Cagliari
Monica Puligheddu - University of Cagliari
Brit Mollenhauer - Paracelsus Elena Klinik Kassel
Claudia Trenkwalder - Paracelsus Elena Klinik Kassel
Friederike Sixel-Döring - Philipps University of Marburg
Christelle Charley Monaca - Centre Hospitalier Universitaire de Lille
Anna Heidbreder - University of Münster
Luigi Ferini-Strambi - Vita-Salute San Raffaele University
Femke Dijkstra - Antwerp University Hospital
Mineke Viaene - 23andMe
Beatriz Abril - 23andMe
Bradley F Boeve - Mayo Clinic in Arizona
Sonja W Scholz - National Institute of Neurological Disorders and Stroke
Mina Ryten - Great Ormond Street Hospital
Sara Bandres-Ciga - National Institute on Aging
Alastair Noyce - Queen Mary University of London
Paul Cannon - 23andMe
Lasse Pihlstrøm - Oslo University Hospital
Mike A Nalls - Data Tecnica International
Andrew B Singleton - National Institutes of Health
Guy A Rouleau - McGill University
Ronald B Postuma - McGill University
Ziv Gan-Or - McGill University
Yves Dauvilliers - Institute for Neurosciences of Montpellier
Valérie Cochen de Cock - Université de Montpellier, EuroMov Digital Health in Motion - EuroMov DHM
Stella Aslibekyan - 23andMe
Adam Auton - 23andMe
Elizabeth Babalola - 23andMe
Robert K Bell - 23andMe
Jessica Bielenberg - 23andMe
Katarzyna Bryc - 23andMe
Emily Bullis - 23andMe
Daniella Coker - 23andMe
Gabriel Cuellar Partida - 23andMe
Devika Dhamija - 23andMe
Sayantan Das - 23andMe
Sarah L Elson - 23andMe
Teresa Filshtein - 23andMe
Kipper Fletez-Brant - 23andMe
Pierre Fontanillas - 23andMe
Will Freyman - 23andMe
Pooja M Gandhi - 23andMe
Barry Hicks - 23andMe
David A Hinds - 23andMe
Ethan M Jewett - 23andMe
Yunxuan Jiang - 23andMe
Katelyn Kukar - 23andMe
Keng-Han Lin - 23andMe
Maya Lowe - 23andMe
Jey C Mccreight - 23andMe
Matthew H Mcintyre - 23andMe
Steven J Micheletti - 23andMe
Meghan E Moreno - 23andMe
Joanna L Mountain - 23andMe
Priyanka Nandakumar - 23andMe
Elizabeth S Noblin - 23andMe
Jared O'Connell - 23andMe
Aaron A Petrakovitz - 23andMe
G David Poznik - 23andMe
Morgan Schumacher - 23andMe
Anjali J Shastri - 23andMe
Janie F Shelton - 23andMe
Jingchunzi Shi - 23andMe
Suyash Shringarpure - 23andMe
Vinh Tran - 23andMe
Joyce Y Tung - 23andMe
Xin Wang - 23andMe
Wei Wang - 23andMe
Catherine H Weldon - 23andMe
Peter Wilton - 23andMe
Alejandro Hernandez - 23andMe
Corinna Wong - 23andMe
Christophe Toukam Tchakouté - 23andMe
Publication Details: Nature Communications, Vol.13(1)
Identifiers: 9940848409311
Academic Unit: Institut des Neurosciences de Montpellier - INM; EuroMov Digital Health in Motion - EuroMov DHM
Language: English
Resource Type: Journal article
Local Fields: hal-04180950