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

Krohn, Lynne; Heilbron, Karl; Blauwendraat, Cornelis; Reynolds, Regina H.; Eric, Yu; Senkevich, Konstantin; Rudakou, Uladzislau; Estiar, Mehrdad A.; Gustavsson, Emil K.; Brolin, Kajsa; Ruskey, Jennifer A.; Freeman, Kathryn; Asayesh, Farnaz; Chia, Ruth; Arnulf, Isabelle; Michele T. M., Hu; Montplaisir, Jacques Y.; Gagnon, Jean-Fran(c(c))ois; Desautels, Alex; Dauvilliers, Yves; Gian Luigi Gigli,; Valente, Mariarosaria; Janes, Francesco; Bernardini, Andrea; Högl, Birgit; Stefani, Ambra; Ibrahim, Abubaker; Karel, ( (S))onka; Kemlink, David; Oertel, Wolfgang; Janzen, Annette; Plazzi, Giuseppe; Biscarini, Francesco; Antelmi, Elena; Figorilli, Michela; Puligheddu, Monica; Mollenhauer, Brit; Trenkwalder, Claudia; Sixel-Döring, Friederike; Val('(e))rie Cochen De Cock,; Christelle Charley Monaca,; Heidbreder, Anna; Ferini-Strambi, Luigi; Dijkstra, Femke; Viaene, Mineke; Abril, Beatriz; Boeve, Bradley F.; Aslibekyan, Stella; Auton, Adam; Babalola, Elizabeth; Bell, Robert K.; Bielenberg, Jessica; Bryc, Katarzyna; Bullis, Emily; Coker, Daniella; Gabriel Cuellar Partida,; 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.; David Poznik, G.; 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; Christophe Toukam Tchakout('(e)),; Scholz, Sonja W.; Ryten, Mina; Bandres-Ciga, Sara; Noyce, Alastair; Cannon, Paul; Pihlstr(o)m, Lasse; Nalls, Mike A.; Singleton, Andrew B.; Rouleau, Guy A.; Postuma, Ronald B.; Ziv Gan-Or and,

doi:10.1038/s41467-022-34732-5

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.

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-Fran{\c{c}}ois Gagnon; Alex Desautels; Yves Dauvilliers; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Andrea Bernardini; Birgit Högl; Ambra Stefani; Abubaker Ibrahim; Karel {\v{S}}onka; David Kemlink; Wolfgang Oertel; Annette Janzen; Giuseppe Plazzi; Francesco Biscarini; Elena Antelmi; Michela Figorilli; Monica Puligheddu; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Döring; Val{\'{e}}rie Cochen De Cock; Christelle Charley Monaca; Anna Heidbreder; Luigi Ferini-Strambi; Femke Dijkstra; Mineke Viaene; Beatriz Abril; Bradley F. Boeve; 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 Tchakout{\'{e}}; Sonja W. Scholz; Mina Ryten; Sara Bandres-Ciga; Alastair Noyce; Paul Cannon; Lasse Pihlstr{\o}m; Mike A. Nalls; Andrew B. Singleton; Guy A. Rouleau; Ronald B. Postuma; Ziv Gan-Or and. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - ELETTRONICO. - 13:1(2022), pp. 7496.1-7496.16. [10.1038/s41467-022-34732-5]