Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
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Krohn, Lynne | Heilbron, Karl | Blauwendraat, Cornelis | Reynolds, Regina, H | Yu, Eric | Senkevich, Konstantin | Rudakou, Uladzislau | Estiar, Mehrdad, A | Gustavsson, Emil, K | Brolin, Kajsa | Ruskey, Jennifer, A | Freeman, Kathryn | Asayesh, Farnaz | Chia, Ruth | Arnulf, Isabelle | Hu, Michele, T M | Montplaisir, Jacques, Y | Gagnon, Jean-François | Desautels, Alex | Gigli, Gian, Luigi | Valente, Mariarosaria | Janes, Francesco | Bernardini, Andrea | Högl, Birgit | Stefani, Ambra | Ibrahim, Abubaker | Šonka, Karel | Kemlink, David | Oertel, Wolfgang | Janzen, Annette | Plazzi, Giuseppe | Biscarini, Francesco | Antelmi, Elena | Figorilli, Michela | Puligheddu, Monica | Mollenhauer, Brit | Trenkwalder, Claudia | Sixel-Döring, Friederike | Monaca, Christelle, Charley | Heidbreder, Anna | Ferini-Strambi, Luigi | Dijkstra, Femke | Viaene, Mineke | Abril, Beatriz | Boeve, Bradley, F | Scholz, Sonja, W | Ryten, Mina | Bandres-Ciga, Sara | Noyce, Alastair | Cannon, Paul | Pihlstrøm, Lasse | Nalls, Mike, A | Singleton, Andrew, B | Rouleau, Guy, A | Postuma, Ronald, B | Gan-Or, Ziv | Dauvilliers, Yves | de Cock, Valérie Cochen | 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
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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.
