Abstract
Isolated/idiopathic rapid-eye movement (REM) sleep behavior disorder (iRBD) is, in most cases, an early form of α -synuclein-related neurodegenerative diseases, including Parkinson’s disease and dementia with Lewy bodies. Clinical reports suggest that iRBD is more common in individuals with Post-Traumatic Stress Disorder (PTSD) compared to those without PTSD. We conducted polygenic risk score (PRS), genetic correlation, and Mendelian randomization analyses to explore potential genetic and/or causal associations between PTSD and iRBD. Dopamine transporter imaging binding status was also examined in iRBD patients with (N = 6) and without PTSD (N = 32). While not supporting a causal relationship, genetic analyses revealed a significant association between PTSD and iRBD, consistent with the exploratory imaging substudy. These findings suggest that individuals genetically at risk for PTSD may also be at higher risk for iRBD. Further investigation of iRBD in individuals with PTSD may help inform potential neurodegenerative risk.
Acknowledgements
This study was financially supported through grants from the Hilary and Galen Weston Foundation, Michael J. Fox Foundation (MJFF) and the Canadian Consortium on Neurodegeneration in Aging (CCNA). Additionally, the G-Can (GBA1-Canada) Initiative, an open-science collaborative initiative aimed at addressing GBA1 mutation-based Parkinson’s disease, has made contributions to this research. G-Can is supported by The Hilary and Galen Weston Foundation, Silverstein Foundation, and J. Sebastian van Berkom and Ghislaine Saucier. This work was supported in part by the Intramural Research Program of the National Institute on Aging (NIA), and the Center for Alzheimer’s and Related Dementias (CARD), within the Intramural Research Program of the National Institute on Aging and the National Institute of Neurological Disorders and Stroke (1ZIAAG000546) as well as NIH NIA grants R34 AG056639, U19 AG071754, P50 AG016574, P30 AG062677 and VA RRD RX004822. M. Skorvanek and K.K. received funding from the Slovak Research and Development Agency under contract no. APVV-22-0279, and the EU Renewal and Resilience Plan “Large projects for excellent researchers” under grant No. 09I03-03-V03-00007. The iRBD cohort study at First Medical Faculty (Prague, Czechia) is supported by the Czech Health Research Council (grant NU21-04-00535) and the National Institute for Neurological Research (Project No. LX22NPO5107), funded by the European Union—Next Generation EU. J.-F.G. holds a Canada Research Chair in Cognitive Decline in Pathological Aging. We acknowledge the contributions of the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD) for support with data sharing. Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG021886) awarded by the National Institute on Aging (NIA), were used in this study. This research used the NeuroHub infrastructure and was undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded through the Healthy Brains, Healthy Lives initiative at McGill University, Calcul Québec and Compute Canada. This research has been conducted using the UK Biobank Resource under Application Number 45551. The UKB cohort was accessed using Neurohub (https://www.mcgill.ca/hbhl/neurohub). Z.G-O. is supported by the Fonds de recherche du Québec—Santé (FRQS) Chercheurs-boursiers award and is a William Dawson Scholar. M.G.S. is supported by a graduate student award, the Jeanne Timmins Costello Award.
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Z.G-O. received consultancy fees from Lysosomal Therapeutics Inc. (LTI), Idorsia, Prevail Therapeutics, Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, Bial Biotech, Bial, UCB, Capsida, Vanqua Bio, Congruence Therapeutics, Takeda, Jazz Pharmaceuticals, EG427, Guidepoint, Lighthouse and Deerfield. Z.G-O. is affiliated with npj Parkinson’s Disease as Associate Editor. Z.G-O. was not involved in the journal’s review of, or decisions related to, this manuscript. B.M. has received honoraria for consultancy and/or educational presentations from GE, Bial, Roche, Biogen, AbbVie, Desitin and Amprion, is a member of the executive steering committee of the Parkinson Progression Marker Initiative of the Michael J. Fox Foundation for Parkinson’s Research and has received research funding from Aligning Science Across Parkinson’s disease (ASAP, CRN). A.D. received research grants from Eisai and Takeda, honoraria from serving on the scientific advisory board of Eisai, Takeda, Paladin Labs, as well as honoraria from speaking engagements from AstraZeneca, Eisai, Jazz Pharma and Paladin Labs. None of the financial disclosures is relevant to the submitted work.
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Ghamgosar Shahkhali, M., Liu, L., Ghamgosar Shahkhali, M.H. et al. Genetic associations between post-traumatic stress disorder and REM-sleep behavior disorder. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01397-6
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DOI: https://doi.org/10.1038/s41531-026-01397-6
