IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34732-5.html
   My bibliography  Save this article

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

Author

Listed:
  • Lynne Krohn

    (McGill University
    McGill University)

  • Karl Heilbron

    (23andMe, Inc.)

  • Cornelis Blauwendraat

    (National Institutes of Health)

  • Regina H. Reynolds

    (University College London
    University College London)

  • Eric Yu

    (McGill University
    McGill University)

  • Konstantin Senkevich

    (McGill University
    McGill University)

  • Uladzislau Rudakou

    (McGill University
    McGill University)

  • Mehrdad A. Estiar

    (McGill University
    McGill University)

  • Emil K. Gustavsson

    (University College London
    University College London)

  • Kajsa Brolin

    (Department of Experimental Medical Science)

  • Jennifer A. Ruskey

    (McGill University)

  • Kathryn Freeman

    (McGill University)

  • Farnaz Asayesh

    (McGill University)

  • Ruth Chia

    (National Institutes of Health)

  • Isabelle Arnulf

    (Paris Brain Insitute and Sorbonne University)

  • Michele T. M. Hu

    (University of Oxford
    University of Oxford)

  • Jacques Y. Montplaisir

    (Hôpital du Sacré-Cœur de Montréal
    Université de Montréal)

  • Jean-François Gagnon

    (Hôpital du Sacré-Cœur de Montréal
    Université du Québec à Montréal)

  • Alex Desautels

    (Hôpital du Sacré-Cœur de Montréal
    Université de Montréal)

  • Yves Dauvilliers

    (Institute Neuroscience Montpellier Inserm)

  • Gian Luigi Gigli

    (University Hospital of Udine)

  • Mariarosaria Valente

    (University Hospital of Udine
    University of Udine)

  • Francesco Janes

    (University Hospital of Udine)

  • Andrea Bernardini

    (University Hospital of Udine)

  • Birgit Högl

    (Medical University of Innsbruck)

  • Ambra Stefani

    (Medical University of Innsbruck)

  • Abubaker Ibrahim

    (Medical University of Innsbruck)

  • Karel Šonka

    (First Faculty of Medicine and General University Hospital)

  • David Kemlink

    (First Faculty of Medicine and General University Hospital)

  • Wolfgang Oertel

    (Philipps-University)

  • Annette Janzen

    (Philipps-University)

  • Giuseppe Plazzi

    (University of Modena and Reggio-Emilia
    Institute of Neurological Sciences of Bologna)

  • Francesco Biscarini

    (University of Bologna)

  • Elena Antelmi

    (Institute of Neurological Sciences of Bologna
    University of Verona)

  • Michela Figorilli

    (University of Cagliari)

  • Monica Puligheddu

    (University of Cagliari)

  • Brit Mollenhauer

    (Paracelsus-Elena-Klinik
    University Medical Centre Goettingen)

  • Claudia Trenkwalder

    (Paracelsus-Elena-Klinik
    University Medical Centre Goettingen)

  • Friederike Sixel-Döring

    (Philipps-University
    Paracelsus-Elena-Klinik)

  • Valérie Cochen De Cock

    (Beau Soleil Clinic
    University of Montpellier IMT Mines Ales)

  • Christelle Charley Monaca

    (CHU Lille)

  • Anna Heidbreder

    (University of Münster)

  • Luigi Ferini-Strambi

    (Università Vita-Salute San Raffaele)

  • Femke Dijkstra

    (St. Dimpna Regional Hospital
    St. Dimpna Regional Hospital
    Antwerp University Hospital)

  • Mineke Viaene

    (St. Dimpna Regional Hospital
    St. Dimpna Regional Hospital)

  • Beatriz Abril

    (University Hospital of Nîmes)

  • Bradley F. Boeve

    (Department of Neurology, Mayo Clinic)

  • Sonja W. Scholz

    (National Institute of Neurological Disorders and Stroke
    Johns Hopkins University Medical Center)

  • Mina Ryten

    (University College London
    University College London)

  • Sara Bandres-Ciga

    (National Institutes of Health)

  • Alastair Noyce

    (Queen Mary University of London
    University College London, Institute of Neurology)

  • Paul Cannon

    (23andMe, Inc.)

  • Lasse Pihlstrøm

    (Oslo University Hospital)

  • Mike A. Nalls

    (Data Tecnica International
    National Institutes of Health)

  • Andrew B. Singleton

    (National Institutes of Health
    National Institutes of Health)

  • Guy A. Rouleau

    (McGill University
    McGill University
    McGill University)

  • Ronald B. Postuma

    (McGill University
    McGill University)

  • Ziv Gan-Or

    (McGill University
    McGill University
    McGill University)

Abstract

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.

Suggested Citation

  • 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. Rus, 2022. "Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34732-5
    DOI: 10.1038/s41467-022-34732-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34732-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34732-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Eun-Jin Bae & Na-Young Yang & Miyoung Song & Cheol Soon Lee & Jun Sung Lee & Byung Chul Jung & He-Jin Lee & Seokjoong Kim & Eliezer Masliah & Sergio Pablo Sardi & Seung-Jae Lee, 2014. "Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    2. Michael J. Hawrylycz & Ed S. Lein & Angela L. Guillozet-Bongaarts & Elaine H. Shen & Lydia Ng & Jeremy A. Miller & Louie N. van de Lagemaat & Kimberly A. Smith & Amanda Ebbert & Zackery L. Riley & Chr, 2012. "An anatomically comprehensive atlas of the adult human brain transcriptome," Nature, Nature, vol. 489(7416), pages 391-399, September.
    3. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    4. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Ziyi Xiong & Xingjian Gao & Yan Chen & Zhanying Feng & Siyu Pan & Haojie Lu & Andre G. Uitterlinden & Tamar Nijsten & Arfan Ikram & Fernando Rivadeneira & Mohsen Ghanbari & Yong Wang & Manfred Kayser , 2022. "Combining genome-wide association studies highlight novel loci involved in human facial variation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Margaret Sunitha Selvaraj & Xihao Li & Zilin Li & Akhil Pampana & David Y. Zhang & Joseph Park & Stella Aslibekyan & Joshua C. Bis & Jennifer A. Brody & Brian E. Cade & Lee-Ming Chuang & Ren-Hua Chung, 2022. "Whole genome sequence analysis of blood lipid levels in >66,000 individuals," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. William R. Reay & Dylan J. Kiltschewskij & Maria A. Biase & Zachary F. Gerring & Kousik Kundu & Praveen Surendran & Laura A. Greco & Erin D. Clarke & Clare E. Collins & Alison M. Mondul & Demetrius Al, 2024. "Genetic influences on circulating retinol and its relationship to human health," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Diptavo Dutta & Yuan He & Ashis Saha & Marios Arvanitis & Alexis Battle & Nilanjan Chatterjee, 2022. "Aggregative trans-eQTL analysis detects trait-specific target gene sets in whole blood," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Tina Roostaei & Hans-Ulrich Klein & Yiyi Ma & Daniel Felsky & Pia Kivisäkk & Sarah M. Connor & Alexandra Kroshilina & Christina Yung & Belinda J. Kaskow & Xiaorong Shao & Brooke Rhead & José M. Ordová, 2021. "Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    8. William J. Young & Jeffrey Haessler & Jan-Walter Benjamins & Linda Repetto & Jie Yao & Aaron Isaacs & Andrew R. Harper & Julia Ramirez & Sophie Garnier & Stefan Duijvenboden & Antoine R. Baldassari & , 2023. "Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. William R. Reay & Michael P. Geaghan & Murray J. Cairns, 2022. "The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. William J. Young & Najim Lahrouchi & Aaron Isaacs & ThuyVy Duong & Luisa Foco & Farah Ahmed & Jennifer A. Brody & Reem Salman & Raymond Noordam & Jan-Walter Benjamins & Jeffrey Haessler & Leo-Pekka Ly, 2022. "Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Seppe Goovaerts & Hanne Hoskens & Ryan J. Eller & Noah Herrick & Anthony M. Musolf & Cristina M. Justice & Meng Yuan & Sahin Naqvi & Myoung Keun Lee & Dirk Vandermeulen & Heather L. Szabo-Rogers & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    12. Thomas S. Wingo & Yue Liu & Ekaterina S. Gerasimov & Selina M. Vattathil & Meghan E. Wynne & Jiaqi Liu & Adriana Lori & Victor Faundez & David A. Bennett & Nicholas T. Seyfried & Allan I. Levey & Aliz, 2022. "Shared mechanisms across the major psychiatric and neurodegenerative diseases," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Max Lam & Chia-Yen Chen & W. David Hill & Charley Xia & Ruoyu Tian & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Alexander S. Hatoum & Hailiang Huang & Anil K. Malhotra & Heiko Runz & Tian Ge, 2022. "Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    14. Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Arianna Landini & Irena Trbojević-Akmačić & Pau Navarro & Yakov A. Tsepilov & Sodbo Z. Sharapov & Frano Vučković & Ozren Polašek & Caroline Hayward & Tea Petrović & Marija Vilaj & Yurii S. Aulchenko &, 2022. "Genetic regulation of post-translational modification of two distinct proteins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    16. Benjamin B. Sun & Stephanie J. Loomis & Fabrizio Pizzagalli & Natalia Shatokhina & Jodie N. Painter & Christopher N. Foley & Megan E. Jensen & Donald G. McLaren & Sai Spandana Chintapalli & Alyssa H. , 2022. "Genetic map of regional sulcal morphology in the human brain from UK biobank data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Sara Larivière & Jessica Royer & Raúl Rodríguez-Cruces & Casey Paquola & Maria Eugenia Caligiuri & Antonio Gambardella & Luis Concha & Simon S. Keller & Fernando Cendes & Clarissa L. Yasuda & Leonardo, 2022. "Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    18. Eeva Sliz & Jaakko S. Tyrmi & Nilufer Rahmioglu & Krina T. Zondervan & Christian M. Becker & Outi Uimari & Johannes Kettunen, 2023. "Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Julia Schröder & Vitalia Schüller & Andrea May & Christian Gerges & Mario Anders & Jessica Becker & Timo Hess & Nicole Kreuser & René Thieme & Kerstin U Ludwig & Tania Noder & Marino Venerito & Lothar, 2019. "Identification of loci of functional relevance to Barrett’s esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with gen," PLOS ONE, Public Library of Science, vol. 14(12), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34732-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.