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Record W4414513611 · doi:10.1038/s41531-025-01078-w

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

2025· article· en· W4414513611 on OpenAlexafffund
Yuri L. Sosero, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe‐Kaufmann, Eric Yu, Uladzislau Rudakou, Jennifer A. Ruskey, Kathryn Freeman, Farnaz Asayesh, Kajsa Brolin, Maria Swanberg, Huw R. Morris, Lesley Wu, Raquel Real, Lasse Pihlstrøm, Manuela Tan, Thomas Gasser, Kathrin Brockmann, Hui Liu, Donald G. Grosset, Simon J.G. Lewis, John B. Kwok, Pau Pástor, Ignacio Álvarez, Matěj Škorvánek, Alexandra Lacková, Miriam Ostrožovičová, Mie Rizig, Lynne Krohn, Ziv Gan‐Or

Bibliographic record

Venuenpj Parkinson s Disease · 2025
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityMcGill Genome CentreMontreal Neurological Institute and Hospital
FundersNIHR Oxford Biomedical Research CentreFonds de Recherche du Québec - SantéOtsuka Pharmaceutical Development and CommercializationNational Institutes of HealthCanada First Research Excellence FundAgentúra na Podporu Výskumu a VývojaUniversity of OxfordParkinson's UKNational Institute of Neurological Disorders and StrokeNational Institute for Health and Care ResearchVerily Life SciencesConsortium canadien en neurodégénérescence associée au vieillissementMcGill UniversityPfizerNHS Greater Glasgow and ClydeCelgeneAligning Science Across Parkinson’sSanofiMichael J. Fox Foundation for Parkinson's ResearchFoundation for the National Institutes of Health
KeywordsREM sleep behavior disorderLinkage disequilibriumDiseaseParkinson's diseaseGenetic associationAssociation (psychology)NeurologyAttention deficit hyperactivity disorderGenetic model

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.280
Teacher spread0.266 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes2
Has abstractyes

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