Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD), the 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 the underlying mechanisms are not well understood. Here we performed a genome-wide association study of RBDs and identified five RBD risk coloci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyzes highlight differential expression of SNCA-AS1 and possibly SCARB2 in different brain regions in RBD, with SNCA-AS1 supported by colocalization analysis. Polygenic risk scoring, pathway analysis, and genetic correlations provide further insight into the genetics of RBD and highlight RBD as a unique subpopulation of alpha-synucleinopathy that will allow for early future intervention.
Ursprache | American English) |
---|---|
article number | 7496 |
diary | nature communication |
Volume | 13 |
issue number | 1 |
Of the | |
Condition | Published -December 2022 |
ASJC Scopus subject areas
- Chemical
- Biochemistry, Genetics and Molecular Biology (all)
- Generally
- Physics and Astronomy (all)
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23andMe Research Team (2022).REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression.nature communication,13(1), [7496].https://doi.org/10.1038/s41467-022-34732-5
REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression./ 23andMe research team.
In:nature communication, Flight. 13, No. 1, 7496, 12.2022.
research result:contribution to the magazine›Article›Peer Review
Research team 23andMe 2022'REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression',nature communication, Flight. 13, no. 1, 7496.https://doi.org/10.1038/s41467-022-34732-5
23andMe research team.REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression.nature communication. December 2022; 13 (1): 7496. two: 10.1038/s41467-022-34732-5
23andMe research team. /REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression. In:nature communication. 2022; Flight. 13, no. 1.
@article{b41aae8fc78a44c2aa60adb9271a059b,
title = "Genome-Wide Association Study of REM Sleep Behavior Disorder Identifies Polygenic Risk and Effects on Brain Expression",
abstract = “Rapid eye movement (REM) sleep behavior disorder (RBD), the representation 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 the underlying mechanisms are not well understood. Here we performed a genome-wide association study of RBDs and identified five RBD risk coloci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyzes highlight differential expression of SNCA-AS1 and possibly SCARB2 in different RBD brain regions, with SNCA-AS1 supported by colocalization analysis. Polygenic risk assessment, pathway analysis, and genetic correlations provide further understanding of the genetics of RBD and highlight RBD as a unique subpopulation of alpha-synucleinopathy that will allow for early future intervention.",
author = "{23andMe Research Team} and Lynne Krohn and Karl Heilbron and Cornelis Blauwendraat and Reynolds, {Regina H.} and Eric Yu and Konstantin Senkevich and Uladzislau Rudakou and Estiar, {Mehrdad A.} and Gustavsson, {Emil K.} and Kajsa Brolin and Ruskey, Jennifer A. and Kathryn Freeman and Farnaz Asayesh and Ruth Chia and Isabelle Arnulf and Hu, Michele TM and Montplaisir, Jacques Y. and Gagnon, Alex Desautels and Yves Dauvilliers and Gigli, Gian Luigi and Mariarosaria Valente and Francesco Janes and Andrea Bernardini and Birgit H{\"ogl and Ambra Stefani and Abubaker Ibrahim and Karel Sonka and David Kemlink and Wolfgang Oertel Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-D{\"o}ring, Val{e}rie and Monaca, Christelle Charley, Anna Heidbreder, Luigi Ferini-Strambi, Femke Dijkstra, Mineke Viaene, Beatriz April Boeve, Bradley F., Stella Aslibekyan, Adam Auton, Elizabeth Babalola,
note = "Funding information: S.W.S. is a member of the Lewy Body Dementia Association Scientific Advisory Board. S.W.S. is a member of the editorial board of JAMA Neurology and the Journal of Parkinson{\textquoteright}s Disease. I.A. was previously a consultant for Idorsia Pharma and UCB Pharma A.D. was a member of the Scientific Advisory Board of Eisai, UCB, Jazz Pharma, has received research support from Jazz Pharma, Flamel Ireland, Canopy Growth and lecture fees from Eisai and Sunovion M.A.N.{\textquoteright} Involved The project was part of a competition agreement arranged by the National Institutes of Health to Data Tecnica International LLC to support open science research. He is also currently a member of Clover Therapeutics' Scientific Advisory Board and is an advisor to Neuron23 Inc as Data Science Fellow.ZGO is recognized by the Chercheurs-boursiers Award from the Fonds de recherche du QuebecSante (FRQS) supports and is a recipient of Canada's New Investigator Award for Parkinson's Disease. He received consulting fees from Ono Therapeutics, Handl Therapeutics, Neuron23, Lysosomal Therapeutics Inc., Bial Biotech Inc., Deerfield, Lighthouse, and Idorsia, all of which were unrelated to this study. KH, PF, and the 23andMe research team are employees of 23andMe, Inc. and have stocks or stock options in 23andMe, Inc. The remaining authors disclose 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 are grateful to the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Neurogenetics Laboratory for their collegiate support and technical assistance. We would like to thank the research participants and 23andMe collaborators 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 Qu{\'e} bec (Doctoral Training Award: L.K.), and Parkinson Canada (Pilot Project Grant :L.K.). In addition, it received support from 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 program. Research from the National Institute on Aging (NIA), the National Institutes of Health, Department of Health and Human Services (project number ZO1 AG000535), and 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 are grateful to the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Neurogenetics Laboratory for their collegiate support and technical assistance. We would like to thank the research participants and 23andMe collaborators 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 Qu{\'e} bec (Doctoral Training Award: L.K.), and Parkinson Canada (Pilot Project Grant :L.K.). In addition, it received support from 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 program. Research from the National Institute on Aging (NIA), the National Institutes of Health, Department of Health and Human Services (project number ZO1 AG000535), and the National Institute of Neurological Disorders and Stroke. Publisher Copyright: {\textcopyright} 2022, the author(s).",
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YOU - LABEL
T1: REM sleep behavior disorder genome-wide association study identifies polygenic risk and effects on brain expression
AU - 23andMe Research Team
AU - Krohn, Lynne
ES - Heilbronn, Karl
ES - Blauwendraat, Cornelis
AU - Reynolds, Regina H.
EN - Yu, Eric
ES - Senkevich, Konstantin
AU - Rudakou, Uladzislau
AU - Estiar, Mehrdad A.
AU - Gustavsson, Emil K.
AU - Brolin, Kajsa
AU - Ruskey, Jennifer A.
Australia - Freeman, Kathryn
AU - Asayesh, Farnaz
ES - Chia, Ruth
EN - Arnulfo, Isabelle
AU-Hu, Michele T.M.
AU - Montplaisir, Jacques Y.
AU - Gagnon, Jean Francois
AU - Desautels, Alex
ES - Dauvilliers, Yves
ES - Gigli, Gian Luigi
AU - Valente, Mariarosaria
EN - Janes, Francesco
EN - Bernardini, Andrea
ES - Högl, Birgit
ES - Stefani, Ambra
ES - Ibrahim, Abubaker
ES - Šonka, Karel
ES - Kemlink, David
ES - Oertel, Wolfgang
ES - Janzen, Annette
ES - Plazzi, Giuseppe
AU - Biscarini, Francesco
EN - Antelmi, Elena
ES - Figorilli, Michela
AU - Puligheddu, Mónica
AU - Mollenhauer, United Kingdom
EN - Trenkwalder, Claudia
ES - Sixel-Döring, Friederike
AU - Cochen De Cock, Valerie
AU - Monaco, Christelle Charley
ES - Heidbreder, Anna
ES - Ferini-Strambi, Luigi
ES - Dijkstra, Femke
AU - Viaene, Maine
AU - April, Beatriz
AU - Boeve, Bradley F.
ES - Aslibekyan, Stella
AU-Auton, Adam
ES - Babalola, Elizabeth
N1 - Financing Information:S.W.S. is a member of the Lewy Body Dementia Association Scientific Advisory Board. SWS is a member of the editorial boards of JAMA Neurology and the Journal of Parkinson's Disease. A.I. he was previously a consultant to Idorsia Pharma and UCB Pharma. A.D. he has served on the Scientific Advisory Boards of Eisai, UCB, Jazz Pharma, received research support from Jazz Pharma, Flamel Ireland, Canopy Growth and speaking fees from Eisai and Sunovion. The participation of M.A.N. in this project he was part of a competitive contract awarded by the National Institutes of Health to Data Tecnica International LLC to support open science research. He is also currently a member of the Scientific Advisory Board for Clover Therapeutics and an advisor to Neuron23 Inc as a data science fellow. ZGO is supported by the Fonds de recherche du QuebecSante (FRQS) Chercheurs-boursiers Prize and is a recipient of Parkinson's Disease Canada's New Investigator Award. He received consulting fees from Ono Therapeutics, Handl Therapeutics, Neuron23, Lysosomal Therapeutics Inc., Bial Biotech Inc., Deerfield, Lighthouse, and Idorsia, all of which were unrelated to this study. KH, PF, and the 23andMe research team are employees of 23andMe, Inc. and have stocks or stock options in 23andMe, Inc. The remaining authors disclose 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 are grateful to the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Neurogenetics Laboratory for their collegiate support and technical assistance. We thank the research participants and collaborators at 23andMe for making this work possible. This work received financial support from 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.). In addition, it received support from 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 program. Research from the National Institute on Aging (NIA), the National Institutes of Health, Department of Health and Human Services (project number ZO1 AG000535), and 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 are grateful to the members of the NINDS Neurodegenerative Diseases Research Unit and the NIA Neurogenetics Laboratory for their collegiate support and technical assistance. We thank the research participants and collaborators at 23andMe for making this work possible. This work received financial support from 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.). In addition, it received support from 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 program. Research from the National Institute on Aging (NIA), the National Institutes of Health, the Department of Health and Human Services (project number ZO1 AG000535), and the National Institute of Neurological Disorders and Stroke. Publisher's Copyright: © 2022, The Author(s).
PJ - 2022/12
Y1 - 2022/12
N2: Rapid eye movement (REM) sleep behavior disorder (RBD), dream representation during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and the underlying mechanisms are not well understood. Here we performed a genome-wide association study of RBDs and identified five RBD risk coloci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyzes highlight differential expression of SNCA-AS1 and possibly SCARB2 in different brain regions in RBD, with SNCA-AS1 supported by colocalization analysis. Polygenic risk scoring, pathway analysis, and genetic correlations provide further insight into the genetics of RBD and highlight RBD as a unique subpopulation of alpha-synucleinopathy that will allow for early future intervention.
AB - Rapid eye movement (REM) sleep behavior disorder (RBD), the 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 the underlying mechanisms are not well understood. Here we performed a genome-wide association study of RBDs and identified five RBD risk coloci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyzes highlight differential expression of SNCA-AS1 and possibly SCARB2 in different brain regions in RBD, with SNCA-AS1 supported by colocalization analysis. Polygenic risk scoring, pathway analysis, and genetic correlations provide further insight into the genetics of RBD and highlight RBD as a unique subpopulation of alpha-synucleinopathy that will allow for early future intervention.
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