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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
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    References listed on IDEAS

    as
    1. 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.
    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. 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.
    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)

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