Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
Lynne Krohn
(1, 2, 3)
,
Karl Heilbron
(3)
,
Cornelis Blauwendraat
(4, 3)
,
Regina H Reynolds
(5, 6, 3)
,
Eric Yu
(1, 2, 3)
,
Konstantin Senkevich
(1, 2, 3)
,
Uladzislau Rudakou
(1, 2, 3)
,
Mehrdad A Estiar
(1, 2, 3)
,
Emil K Gustavsson
(6, 7, 3)
,
Kajsa Brolin
(8, 3)
,
Jennifer A Ruskey
(2, 3)
,
Kathryn Freeman
(2, 3)
,
Farnaz Asayesh
(2, 3)
,
Ruth Chia
(4, 3)
,
Isabelle Arnulf
(9, 3)
,
Michele T M Hu
(10, 11, 3)
,
Jacques Y Montplaisir
(12, 13, 3)
,
Jean-François Gagnon
(12, 14, 3)
,
Alex Desautels
(12, 13, 3)
,
Gian Luigi Gigli
(15, 3)
,
Mariarosaria Valente
(15, 3)
,
Francesco Janes
(15, 3)
,
Andrea Bernardini
(15, 3)
,
Birgit Högl
(16, 3)
,
Ambra Stefani
(16, 3)
,
Abubaker Ibrahim
(16, 3)
,
Karel Šonka
(17, 3)
,
David Kemlink
(17, 3)
,
Wolfgang Oertel
(18, 3)
,
Annette Janzen
(18, 3)
,
Giuseppe Plazzi
(19, 20, 3)
,
Francesco Biscarini
(21, 3)
,
Elena Antelmi
(20, 22, 3)
,
Michela Figorilli
(23, 3)
,
Monica Puligheddu
(23, 3)
,
Brit Mollenhauer
(24, 25, 3)
,
Claudia Trenkwalder
(24, 25, 3)
,
Friederike Sixel-Döring
(18, 24, 3)
,
Christelle Charley Monaca
(26, 3)
,
Anna Heidbreder
(27, 3)
,
Luigi Ferini-Strambi
(28, 3)
,
Femke Dijkstra
(29, 30, 3)
,
Mineke Viaene
(29, 3)
,
Beatriz Abril
(31, 3)
,
Bradley F Boeve
(32, 3)
,
Sonja W Scholz
(33, 34, 3)
,
Mina Ryten
(6, 7, 3)
,
Sara Bandres-Ciga
(4, 3)
,
Alastair Noyce
(35, 36, 3)
,
Paul Cannon
(3)
,
Lasse Pihlstrøm
(37, 3)
,
Mike A Nalls
(38, 4, 3)
,
Andrew B Singleton
(4, 3)
,
Guy A Rouleau
(1, 2, 3)
,
Ronald B Postuma
(2, 1, 3)
,
Ziv Gan-Or
(1, 2, 3)
,
Yves Dauvilliers
(39, 40, 3)
,
Valérie Cochen de Cock
(41, 42, 3)
,
Stella Aslibekyan
(3)
,
Adam Auton
(3)
,
Elizabeth Babalola
(3)
,
Robert K Bell
(3)
,
Jessica Bielenberg
(3)
,
Katarzyna Bryc
(3)
,
Emily Bullis
(3)
,
Daniella Coker
(3)
,
Gabriel Cuellar Partida
(3)
,
Devika Dhamija
(3)
,
Sayantan Das
(3)
,
Sarah L Elson
(3)
,
Teresa Filshtein
(3)
,
Kipper Fletez-Brant
(3)
,
Pierre Fontanillas
(3)
,
Will Freyman
(3)
,
Pooja M Gandhi
(3)
,
Barry Hicks
(3)
,
David A Hinds
(3)
,
Ethan M Jewett
(3)
,
Yunxuan Jiang
(3)
,
Katelyn Kukar
(3)
,
Keng-Han Lin
(3)
,
Maya Lowe
(3)
,
Jey C Mccreight
(3)
,
Matthew H Mcintyre
(3)
,
Steven J Micheletti
(3)
,
Meghan E Moreno
(3)
,
Joanna L Mountain
(3)
,
Priyanka Nandakumar
(3)
,
Elizabeth S Noblin
(3)
,
Jared O'Connell
(3)
,
Aaron A Petrakovitz
(3)
,
G David Poznik
(3)
,
Morgan Schumacher
(3)
,
Anjali J Shastri
(3)
,
Janie F Shelton
(3)
,
Jingchunzi Shi
(3)
,
Suyash Shringarpure
(3)
,
Vinh Tran
(3)
,
Joyce Y Tung
(3)
,
Xin Wang
(3)
,
Wei Wang
(3)
,
Catherine H Weldon
(3)
,
Peter Wilton
(3)
,
Alejandro Hernandez
(3)
,
Corinna Wong
(3)
,
Christophe Toukam Tchakouté
(3)
1
McGill University = Université McGill [Montréal, Canada]
2 Montreal Neurological Institute and Hospital
3 23andMe Inc.
4 NIH - National Institutes of Health [Bethesda, MD, USA]
5 UCL - University College of London [London]
6 UCL - Great Ormond Street Institute of Child Health
7 GOSHC - Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK]
8 Lund University
9 CHU Pitié-Salpêtrière [AP-HP]
10 Oxford e-Research Centre [Oxford]
11 Nuffield Department of Clinical Neurosciences [Oxford]
12 CEAMS - Centre d'études avancées en Médecine du Sommeil
13 UdeM - Université de Montréal
14 UQAM - Université du Québec à Montréal = University of Québec in Montréal
15 Università degli Studi di Udine - University of Udine [Italie]
16 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
17 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
18 Philipps Universität Marburg = Philipps University of Marburg
19 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
20 Institute of Neurological Sciences of Bologna IRCCS
21 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
22 UNIVR - Università degli studi di Verona = University of Verona
23 UniCa - Università degli Studi di Cagliari = University of Cagliari
24 Paracelsus-Elena-Klinik, Kassel, Germany.
25 UMG - University Medical Center Göttingen
26 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
27 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
28 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
29 St. Dimpna Regional Hospital (Geel)
30 UZA - Antwerp University Hospital [Edegem]
31 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
32 Mayo Clinic [Rochester]
33 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
34 Johns Hopkins University School of Medicine [Baltimore]
35 QMUL - Queen Mary University of London
36 UCLH - University College London Hospitals
37 Oslo University Hospital [Oslo]
38 Data Tecnica International
39 Département de Neurologie [Hôpital Gui de Chauliac - CHU Montpellier]
40 INM - Institut des Neurosciences de Montpellier
41 Euromov DHM - EuroMov - Digital Health in Motion
42 Clinique Médicale Beausoleil
2 Montreal Neurological Institute and Hospital
3 23andMe Inc.
4 NIH - National Institutes of Health [Bethesda, MD, USA]
5 UCL - University College of London [London]
6 UCL - Great Ormond Street Institute of Child Health
7 GOSHC - Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK]
8 Lund University
9 CHU Pitié-Salpêtrière [AP-HP]
10 Oxford e-Research Centre [Oxford]
11 Nuffield Department of Clinical Neurosciences [Oxford]
12 CEAMS - Centre d'études avancées en Médecine du Sommeil
13 UdeM - Université de Montréal
14 UQAM - Université du Québec à Montréal = University of Québec in Montréal
15 Università degli Studi di Udine - University of Udine [Italie]
16 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
17 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
18 Philipps Universität Marburg = Philipps University of Marburg
19 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
20 Institute of Neurological Sciences of Bologna IRCCS
21 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
22 UNIVR - Università degli studi di Verona = University of Verona
23 UniCa - Università degli Studi di Cagliari = University of Cagliari
24 Paracelsus-Elena-Klinik, Kassel, Germany.
25 UMG - University Medical Center Göttingen
26 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
27 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
28 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
29 St. Dimpna Regional Hospital (Geel)
30 UZA - Antwerp University Hospital [Edegem]
31 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
32 Mayo Clinic [Rochester]
33 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
34 Johns Hopkins University School of Medicine [Baltimore]
35 QMUL - Queen Mary University of London
36 UCLH - University College London Hospitals
37 Oslo University Hospital [Oslo]
38 Data Tecnica International
39 Département de Neurologie [Hôpital Gui de Chauliac - CHU Montpellier]
40 INM - Institut des Neurosciences de Montpellier
41 Euromov DHM - EuroMov - Digital Health in Motion
42 Clinique Médicale Beausoleil
Cornelis Blauwendraat
- Fonction : Auteur
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- ORCID : 0000-0001-9358-8111
Regina H Reynolds
- Fonction : Auteur
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Eric Yu
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Emil K Gustavsson
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Kathryn Freeman
- Fonction : Auteur
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Ruth Chia
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Isabelle Arnulf
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Andrea Bernardini
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Karel Šonka
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Monica Puligheddu
- Fonction : Auteur
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Bradley F Boeve
- Fonction : Auteur
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Sonja W Scholz
- Fonction : Auteur
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Mina Ryten
- Fonction : Auteur
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Alastair Noyce
- Fonction : Auteur
- PersonId : 1275784
- ORCID : 0000-0003-3027-5497
Guy A Rouleau
- Fonction : Auteur
- PersonId : 764544
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Ziv Gan-Or
- Fonction : Auteur
- PersonId : 791221
- ORCID : 0000-0003-0332-234X
Yves Dauvilliers
- Fonction : Auteur
- PersonId : 758941
- ORCID : 0000-0003-0683-6506
Valérie Cochen de Cock
- Fonction : Auteur
- PersonId : 1136432
- IdHAL : valerie-cochen
- ORCID : 0000-0002-6460-4319
Résumé
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.
Domaines
Neurosciences [q-bio.NC]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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Licence |