Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
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Published:2022-12-05
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Krohn Lynne, Heilbron Karl, Blauwendraat CornelisORCID, Reynolds Regina H.ORCID, Yu EricORCID, Senkevich Konstantin, Rudakou Uladzislau, Estiar Mehrdad A., Gustavsson Emil K.ORCID, Brolin Kajsa, Ruskey Jennifer A., Freeman KathrynORCID, Asayesh Farnaz, Chia RuthORCID, Arnulf IsabelleORCID, Hu Michele T. M., Montplaisir Jacques Y., Gagnon Jean-François, Desautels Alex, Dauvilliers Yves, Gigli Gian Luigi, Valente Mariarosaria, Janes Francesco, Bernardini AndreaORCID, Högl Birgit, Stefani Ambra, Ibrahim Abubaker, Šonka KarelORCID, Kemlink David, Oertel Wolfgang, Janzen Annette, Plazzi Giuseppe, Biscarini Francesco, Antelmi Elena, Figorilli Michela, Puligheddu MonicaORCID, Mollenhauer Brit, Trenkwalder Claudia, Sixel-Döring Friederike, Cochen De Cock Valérie, Monaca Christelle Charley, Heidbreder Anna, Ferini-Strambi Luigi, Dijkstra Femke, Viaene Mineke, Abril Beatriz, Boeve Bradley F.ORCID, Aslibekyan Stella, Auton Adam, Babalola Elizabeth, Bell Robert K., Bielenberg Jessica, Bryc Katarzyna, Bullis Emily, Coker Daniella, Partida Gabriel Cuellar, Dhamija Devika, Das Sayantan, Elson Sarah L., Filshtein Teresa, Fletez-Brant Kipper, Fontanillas Pierre, Freyman Will, Gandhi Pooja M., Hicks Barry, Hinds David A., Jewett Ethan M., Jiang Yunxuan, Kukar Katelyn, Lin Keng-Han, Lowe Maya, McCreight Jey C., McIntyre Matthew H., Micheletti Steven J., Moreno Meghan E., Mountain Joanna L., Nandakumar Priyanka, Noblin Elizabeth S., O’Connell Jared, Petrakovitz Aaron A., Poznik G. David, Schumacher Morgan, Shastri Anjali J., Shelton Janie F., Shi Jingchunzi, Shringarpure Suyash, Tran Vinh, Tung Joyce Y., Wang Xin, Wang Wei, Weldon Catherine H., Wilton Peter, Hernandez Alejandro, Wong Corinna, Tchakouté Christophe Toukam, Scholz Sonja W.ORCID, Ryten MinaORCID, Bandres-Ciga Sara, Noyce AlastairORCID, Cannon Paul, Pihlstrøm Lasse, Nalls Mike A., Singleton Andrew B., Rouleau Guy A.ORCID, Postuma Ronald B., Gan-Or ZivORCID,
Abstract
AbstractRapid-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.
Funder
Michael J. Fox Foundation for Parkinson’s Research Parkinson Canada Fonds de Recherche du Québec-Société et Culture Foundation for the National Institutes of Health
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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