Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links

Morvarid Ghamgosar Shahkhali; Lang Liu; Mohammad H. Ghamgosar Shahkhali; Eric Yu; Farnaz Asayesh; Jamil Ahmad; Meron Teferra; Isabelle Arnulf; Pauline Dodet; Yo-El Ju; Michele T.M. Hu; Jacques Y. Montplaisir; Jean-François Gagnon; Alex Desautels; Abubaker Ibrahim; Ambra Stefani; Birgit Högl; Merve Akrtan-Süzgün; Alex Iranzo; Mónica Serradell; Angelica Montini; Gerard Maya; Carles Gaig; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Andrea Bernardini; Yves Dauvilliers; Karel Sonka; David Kemlink; Petr Dusek; Michael Sommerauer; Gültekin Tamgüney; Michela Figorilli; Monica Puligheddu; Valerie Cochen De Cock; Wolfgang Oertel; Annette Janzen; Elena Antelmi; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Doring; Michele Terzaghi; Giuseppe Fiamingo; Matej Skorvanek; Kristina Kulcsarova; Beatriz Abril; Christelle Charley Monaca; Luigi Ferini-Strambi; Jitka Bušková; Beatrice Orso; Pietro Mattioli; Dario Arnaldi; Femke Dijkstra; Mineke Viaene; Bradley F. Boeve; Owen A. Ross; Guy A. Rouleau; Lee E. Neilson; Jonathan E. Elliott; Miranda M. Lim; Ronald B. Postuma; Ziv Gan-Or

doi:10.1101/2025.09.05.25335205

Prépublication

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links

Morvarid Ghamgosar Shahkhali, Lang Liu, Mohammad H. Ghamgosar Shahkhali, Eric Yu, Farnaz Asayesh, Jamil Ahmad, Meron Teferra, Isabelle Arnulf, Pauline Dodet, Yo-El Ju, …

medRxiv

Cold Spring Harbor Laboratory Press, 1.1

08/09/2025

DOI: https://doi.org/10.1101/2025.09.05.25335205

PMID: 40963755

Résumé

Genetic and Genomic Medicine

To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status—a marker of neurodegeneration—in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.

Indicateurs

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Détails

Titre: Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links
Créateurs - sans rôle: Morvarid Ghamgosar Shahkhali - Department of Human Genetics, McGill University
Lang Liu - Department of Neurology and Neurosurgery, McGill University
Mohammad H. Ghamgosar Shahkhali - Department of Computer Engineering, Ahrar Institute of Technology and Higher Education
Eric Yu - McGill University
Farnaz Asayesh - McGill University
Jamil Ahmad - McGill University
Meron Teferra - Department of Neurology and Neurosurgery, McGill University
Isabelle Arnulf - Sleep Clinic, Pitié Salpêtrière hospital, APHP-Sorbonne University and Paris Brain institute
Pauline Dodet - Pitié-Salpêtrière Hospital
Yo-El Ju - Department of Neurology, Washington University School of Medicine
Michele T.M. Hu - Nuffield Department of Clinical Neurosciences, University of Oxford
Jacques Y. Montplaisir - Université de Montréal
Jean-François Gagnon - Department of Psychology, Université du Québec à Montréal
Alex Desautels - Université de Montréal
Abubaker Ibrahim - Department of Neurology, Sleep Disorders Clinic, Medical University of Innsbruck
Ambra Stefani - Department of Neurology, Sleep Disorders Clinic, Medical University of Innsbruck
Birgit Högl - Department of Neurology, Sleep Disorders Clinic, Medical University of Innsbruck
Merve Akrtan-Süzgün - Department of Neurology, Sleep Disorders Clinic, Medical University of Innsbruck
Alex Iranzo - Sleep Centre, Hospital Clínic Barcelona
Mónica Serradell - Sleep Centre, Hospital Clínic Barcelona
Angelica Montini - Sleep Centre, Hospital Clínic Barcelona
Gerard Maya - Sleep Centre, Hospital Clínic Barcelona
Carles Gaig - Sleep Centre, Hospital Clínic Barcelona
Gian Luigi Gigli - Department of Medicine (DMED), University of Udine
Mariarosaria Valente - University of Udine
Francesco Janes - University of Udine
Andrea Bernardini - University of Udine
Yves Dauvilliers - Institute for Neurosciences of Montpellier
Karel Sonka - Charles University
David Kemlink - Charles University
Petr Dusek - Charles University
Michael Sommerauer - University Hospital of Bonn
Gültekin Tamgüney - Heinrich-Heine-Universität Düsseldorf
Michela Figorilli - University of Cagliari
Monica Puligheddu - University of Cagliari
Valerie Cochen De Cock - EuroMov Digital Health in Motion
Wolfgang Oertel - Department of Neurology, Philipps-University
Annette Janzen - Department of Neurology, Philipps-University
Elena Antelmi - DIMI Department of Engineering and Medicine of Innovation, University of Verona
Brit Mollenhauer - Paracelsus-Elena-Klinik
Claudia Trenkwalder - Paracelsus-Elena-Klinik
Friederike Sixel-Doring - Department of Neurology, University Medical Centre Göttingen
Michele Terzaghi - University of Pavia
Giuseppe Fiamingo - University of Pavia
Matej Skorvanek - Department of Clinical Neurosciences, Faculty of Medicine, P. J. Safarik University
Kristina Kulcsarova - Department of Clinical Neurosciences, Faculty of Medicine, P. J. Safarik University
Beatriz Abril - Carémeau Hospital, University Hospital of Nîmes
Christelle Charley Monaca - Department of Clinical Neurophysiology and Sleep Center, University Lille North of France
Luigi Ferini-Strambi - Department of Neurological Sciences, Università Vita-Salute San Raffaele
Jitka Bušková - Charles University
Beatrice Orso - Department of Neuroscience (DINOGMI), University of Genoa
Pietro Mattioli - Ospedale Policlinico San Martino
Dario Arnaldi - Ospedale Policlinico San Martino
Femke Dijkstra - Department of Neurology, Antwerp University Hospital
Mineke Viaene - Department of Neurology, St. Dimpna Regional Hospital
Bradley F. Boeve - Mayo Clinic
Owen A. Ross - Mayo Clinic
Guy A. Rouleau - McGill University
Lee E. Neilson - Department of Veteran Affairs, VA Portland Health Care System and VISN20 Northwest Mental Illness Research, Education, and Clinical Center
Jonathan E. Elliott - Department of Veteran Affairs, VA Portland Health Care System and VISN20 Northwest Mental Illness Research, Education, and Clinical Center
Miranda M. Lim - Department of Veteran Affairs, VA Portland Health Care System and VISN20 Northwest Mental Illness Research, Education, and Clinical Center
Ronald B. Postuma - Centre d’Études Avancées en Médecine du Sommeil
Ziv Gan-Or - Department of Neurology and Neurosurgery, McGill University
Détails de publication: medRxiv
Éditeur: Cold Spring Harbor Laboratory Press
Édition: 1.1
Nombre de pages: 20
Identifiants: 99140105209311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Preprint