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

Sosero, Yuri L. ; Heilbron, Karl ; Fontanillas, Pierre ; Norcliffe-Kaufmann, Lucy ; Yu, Eric ; Rudakou, Uladzislau ; Ruskey, Jennifer A. ; Freeman, Kathryn ; Asayesh, Farnaz and Brolin, Kajsa A. LU orcid , et al. (2025) In npj Parkinson's Disease 11(1).
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 =... (More)

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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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
npj Parkinson's Disease
volume
11
issue
1
article number
272
publisher
Springer Nature
external identifiers
  • scopus:105018471518
  • pmid:40998812
ISSN
2373-8057
DOI
10.1038/s41531-025-01078-w
language
English
LU publication?
yes
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Publisher Copyright: © The Author(s) 2025.
id
c0dc2600-c7c0-430e-8617-ed6d6f07bb99
date added to LUP
2025-12-11 09:22:09
date last changed
2025-12-12 03:33:21
@article{c0dc2600-c7c0-430e-8617-ed6d6f07bb99,
  abstract     = {{<p>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.</p>}},
  author       = {{Sosero, Yuri L. and Heilbron, Karl and Fontanillas, Pierre and Norcliffe-Kaufmann, Lucy and Yu, Eric and Rudakou, Uladzislau and Ruskey, Jennifer A. and Freeman, Kathryn and Asayesh, Farnaz and Brolin, Kajsa A. and Swanberg, Maria and Morris, Huw R. and Wu, Lesley and Real, Raquel and Pihlstrøm, Lasse and Tan, Manuela and Gasser, Thomas and Brockmann, Kathrin and Liu, Hui and Hu, Michele T.M. and Grosset, Donald G. and Lewis, Simon J.G. and Kwok, John B. and Pastor, Pau and Alvarez, Ignacio and Skorvanek, Matej and Lackova, Alexandra and Ostrozovicova, Miriam and Rizig, Mie and Krohn, Lynne and Gan-Or, Ziv}},
  issn         = {{2373-8057}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{npj Parkinson's Disease}},
  title        = {{Genome-wide association study of REM sleep behavior disorder in Parkinson’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41531-025-01078-w}},
  doi          = {{10.1038/s41531-025-01078-w}},
  volume       = {{11}},
  year         = {{2025}},
}