Genome-wide association study of REM sleep behavior disorder in Parkinson’s disease

REM sleep behavior disorder (RBD), is a prodromal synucleinopathy affecting a subset of Parkinson's disease (PD) patients and associated with neuropsychiatric symptoms. This study compared the genetic profiles of 13,020 PD patients with probable RBD (PD + RBD) and 5403 without (PD-RBD) using genome-wide association study (GWAS). RBD was assessed by questionnaires or self-reporting. Potential genetic correlations between neuropsychiatric traits and PD + RBD were assessed using linkage disequilibrium score regression. The top variant in the SNCA locus was associated with PD + RBD (rs10005233-T, OR = 1.21, 95% CI = 1.16-1.27, p = 1.81e-15). PD risk variants in SNCA (rs5019538-G, OR = 0.85, 95% CI = 0.81-0.89, p = 2.46e-10; rs356182-G, OR = 0.89, 95% CI = 0.84-0.95, p = 0.0001) and LRRK2 loci (rs34637584, OR = 0.41, 95% CI = 0.28-0.61, p = 1.04e-5) were associated with reduced PD + RBD risk. A suggestive genetic correlation between attention deficit hyperactivity disorder and PD + RBD was observed but was not statistically significant after correction. These findings highlight genetic distinctions between PD + RBD and PD-RBD, offering insights into PD stratification and potential subtype-specific treatments.

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Publication Details

Journal
npj Parkinson s Disease
Published
2025-09-25
DOI
https://doi.org/10.1038/s41531-025-01078-w
Citations
1
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
1.39

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Genome-wide association study of REM sleep behavior disorder in Parkinson’s disease

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Parkinson's Disease Mechanisms and Treatments
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article

Genome-wide association study of REM sleep behavior disorder in Parkinson’s disease

Raquel Real, Uladzislau Rudakou, Kathrin Brockmann, Kajsa Brolin, Ignacio Álvarez, Farnaz Asayesh, John B. Kwok, Lesley Wu, Pau Pástor, Jennifer A. Ruskey, Manuela Tan, Yuri L. Sosero, Maria Swanberg, Lynne Krohn, Miriam Ostrožovičová, Donald G. Grosset, Lasse Pihlstrøm, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe‐Kaufmann, Thomas Gasser, Mie Rizig, Eric Yu, Huw R. Morris, Alexandra Lacková, Kathryn Freeman, Simon J.G. Lewis, Matěj Škorvánek, Ziv Gan‐Or, Hui Liu
article en
1 citations

Abstract

REM sleep behavior disorder (RBD), is a prodromal synucleinopathy affecting a subset of Parkinson's disease (PD) patients and associated with neuropsychiatric symptoms. This study compared the genetic profiles of 13,020 PD patients with probable RBD (PD + RBD) and 5403 without (PD-RBD) using genome-wide association study (GWAS). RBD was assessed by questionnaires or self-reporting. Potential genetic correlations between neuropsychiatric traits and PD + RBD were assessed using linkage disequilibrium score regression. The top variant in the SNCA locus was associated with PD + RBD (rs10005233-T, OR = 1.21, 95% CI = 1.16-1.27, p = 1.81e-15). PD risk variants in SNCA (rs5019538-G, OR = 0.85, 95% CI = 0.81-0.89, p = 2.46e-10; rs356182-G, OR = 0.89, 95% CI = 0.84-0.95, p = 0.0001) and LRRK2 loci (rs34637584, OR = 0.41, 95% CI = 0.28-0.61, p = 1.04e-5) were associated with reduced PD + RBD risk. A suggestive genetic correlation between attention deficit hyperactivity disorder and PD + RBD was observed but was not statistically significant after correction. These findings highlight genetic distinctions between PD + RBD and PD-RBD, offering insights into PD stratification and potential subtype-specific treatments.

npj Parkinson s DiseaseVol. 11(1)
Oslo University Hospital (NO), Montreal Neurological Institute and Hospital (CA), The University of Sydney (AU), Lund University (SE), University of Pavol Jozef Šafárik (SK), University of Oxford (GB), 23andMe (United States) (US), Parkinson's UK (GB), Univerzitná Nemocnica Louisa Pasteura (SK), McGill Genome Centre (CA), Mútua Terrassa (ES), Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES), Hertie Institute for Clinical Brain Research (DE), National Hospital for Neurology and Neurosurgery (GB), Queen Elizabeth University Hospital (GB), University College London (GB), McGill University (CA)
Foundation for the National Institutes of Health, Michael J. Fox Foundation for Parkinson's Research, Pfizer, Sanofi, Celgene, McGill University, NHS Greater Glasgow and Clyde, Consortium canadien en neurodégénérescence associée au vieillissement, Verily Life Sciences, National Institute for Health and Care Research, Parkinson's UK, University of Oxford, Agentúra na Podporu Výskumu a Vývoja, Canada First Research Excellence Fund, National Institutes of Health, Otsuka Pharmaceutical Development and Commercialization, Fonds de Recherche du Québec - Santé, NIHR Oxford Biomedical Research Centre, National Institute of Neurological Disorders and Stroke
Openalex Percentile: Top 15%
Parkinson's Disease Mechanisms and Treatments
1.39
DOIOpen Access PDFOpenAlex
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