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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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| 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 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Krohn, Lynne |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-9722930 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-97229302022-12-07 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. 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 Nat Commun Article 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. Nature Publishing Group UK 2022-12-05 /pmc/articles/PMC9722930/ /pubmed/36470867 http://dx.doi.org/10.1038/s41467-022-34732-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article 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 Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title | Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title_full | Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title_fullStr | Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title_full_unstemmed | Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title_short | Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects |
| title_sort | genome-wide association study of rem sleep behavior disorder identifies polygenic risk and brain expression effects |
| topic | Article |
| url | 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 |
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