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

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...

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Detalles Bibliográficos
Autores principales: 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, Dauvilliers, Yves, 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, Cochen De Cock, Valérie, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722930/
https://www.ncbi.nlm.nih.gov/pubmed/36470867
http://dx.doi.org/10.1038/s41467-022-34732-5
Descripción
Sumario: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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