TY - JOUR
T1 - Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
AU - 23andMe Research Team
AU - Krohn, Lynne
AU - Heilbron, Karl
AU - Blauwendraat, Cornelis
AU - Reynolds, Regina H.
AU - Yu, Eric
AU - Senkevich, Konstantin
AU - Rudakou, Uladzislau
AU - Estiar, Mehrdad A.
AU - Gustavsson, Emil K.
AU - Brolin, Kajsa
AU - Ruskey, Jennifer A.
AU - Freeman, Kathryn
AU - Asayesh, Farnaz
AU - Chia, Ruth
AU - Arnulf, Isabelle
AU - Hu, Michele T.M.
AU - Montplaisir, Jacques Y.
AU - Gagnon, Jean François
AU - Desautels, Alex
AU - Dauvilliers, Yves
AU - Gigli, Gian Luigi
AU - Valente, Mariarosaria
AU - Janes, Francesco
AU - Bernardini, Andrea
AU - Högl, Birgit
AU - Stefani, Ambra
AU - Ibrahim, Abubaker
AU - Šonka, Karel
AU - Kemlink, David
AU - Oertel, Wolfgang
AU - Janzen, Annette
AU - Plazzi, Giuseppe
AU - Biscarini, Francesco
AU - Antelmi, Elena
AU - Figorilli, Michela
AU - Puligheddu, Monica
AU - Mollenhauer, Brit
AU - Trenkwalder, Claudia
AU - Sixel-Döring, Friederike
AU - Cochen De Cock, Valérie
AU - Monaca, Christelle Charley
AU - Heidbreder, Anna
AU - Ferini-Strambi, Luigi
AU - Dijkstra, Femke
AU - Viaene, Mineke
AU - Abril, Beatriz
AU - Boeve, Bradley F.
AU - Aslibekyan, Stella
AU - Auton, Adam
AU - Babalola, Elizabeth
N1 - Funding Information:
S.W.S. serves on the Scientific Advisory Council of the Lewy Body Dementia Association. S.W.S. is an editorial board member for JAMA Neurology and the Journal of Parkinson’s Disease. I.A. was previously consultant for Idorsia pharma, and UCB Pharma. A.D. served on the scientific advisory board for Eisai, UCB, Jazz Pharma, received research support from Jazz Pharma, Flamel Ireland, Canopy Growth, and honoraria from speaking engagements from Eisai and Sunovion. M.A.N.’s participation in this project was part of a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research, he also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc as a data science fellow. Z.G.O. is supported by the Fonds de recherche du QuebecSante (FRQS) Chercheurs-boursiers award, and is a Parkinson’s Disease Canada New Investigator awardee. He received consultancy fees from Ono Therapeutics, Handl Therapeutics, Neuron23, Lysosomal Therapeutics Inc., Bial Biotech Inc., Deerfield, Lighthouse, and Idorsia, all unrelated to the current study. K.H., P.F., and the 23andMe Research Team are employed by and hold stock or stock options in 23andMe, Inc. The remaining authors declare no competing interests.
Funding Information:
HYPERGENES Project: https://cordis.europa.eu/project/rcn/86758_en.html Wellcome Trust Case Control Consortium: https://www.wtccc.org.uk/ . We thank the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Laboratory of Neurogenetic for their collegial support and technical assistance. We would like to thank the research participants and employees of 23andMe for making this work possible This work was financially supported by the Michael J. Fox Foundation (MJFF-020700: Z.G-O.), Fonds de recherche du Québec (Doctoral Training Award: L.K.), and Parkinson Canada (Pilot Project Grant: L.K.). It was additionally supported by the Canadian Consortium on Neurodegeneration in Aging (CCNA), and the Canada First Research Excellence Fund (CFREF) awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program, and was supported in part by the Intramural Research Program of the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services (project number ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke.
Funding Information:
HYPERGENES Project: https://cordis.europa.eu/project/rcn/86758_en.html Wellcome Trust Case Control Consortium: https://www.wtccc.org.uk/. We thank the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Laboratory of Neurogenetic for their collegial support and technical assistance. We would like to thank the research participants and employees of 23andMe for making this work possible This work was financially supported by the Michael J. Fox Foundation (MJFF-020700: Z.G-O.), Fonds de recherche du Québec (Doctoral Training Award: L.K.), and Parkinson Canada (Pilot Project Grant: L.K.). It was additionally supported by the Canadian Consortium on Neurodegeneration in Aging (CCNA), and the Canada First Research Excellence Fund (CFREF) awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program, and was supported in part by the Intramural Research Program of the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services (project number ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-34732-5
DO - 10.1038/s41467-022-34732-5
M3 - Article
C2 - 36470867
AN - SCOPUS:85143480320
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7496
ER -