The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease

Autores
Perez Lloret, Santiago; Chevalier, Guenson; Bordet, Sofía; Barbar, Hanny; Capani, Francisco; Udovin, Lucas; Otero losada, Matilde Estela
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.
Fil: Perez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; Argentina
Fil: Barbar, Hanny. Universidad Abierta Interamericana; Argentina
Fil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
REM-SLEEP BEHAVIOR DISORDERS
SINGLE NUCLEOTIDE POLYMORPHISM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/220903
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/220903
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s DiseasePerez Lloret, SantiagoChevalier, GuensonBordet, SofíaBarbar, HannyCapani, FranciscoUdovin, LucasOtero losada, Matilde EstelaPARKINSON’S DISEASEPATHOPHYSIOLOGYPD-RELATED VARIANTSREM-SLEEP BEHAVIOR DISORDERSSINGLE NUCLEOTIDE POLYMORPHISMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.Fil: Perez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; ArgentinaFil: Barbar, Hanny. Universidad Abierta Interamericana; ArgentinaFil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2023-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/220903Perez Lloret, Santiago; Chevalier, Guenson; Bordet, Sofía; Barbar, Hanny; Capani, Francisco; et al.; The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease; MDPI; Brain Sciences; 13; 8; 8-2023; 1-142076-3425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci13081146info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:04Zoai:ri.conicet.gov.ar:11336/220903instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:05.151CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
spellingShingle The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
Perez Lloret, Santiago
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
REM-SLEEP BEHAVIOR DISORDERS
SINGLE NUCLEOTIDE POLYMORPHISM
title_short The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_full The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_fullStr The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_full_unstemmed The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_sort The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
dc.creator.none.fl_str_mv Perez Lloret, Santiago
Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero losada, Matilde Estela
author Perez Lloret, Santiago
author_facet Perez Lloret, Santiago
Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero losada, Matilde Estela
author_role author
author2 Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero losada, Matilde Estela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
REM-SLEEP BEHAVIOR DISORDERS
SINGLE NUCLEOTIDE POLYMORPHISM
topic PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
REM-SLEEP BEHAVIOR DISORDERS
SINGLE NUCLEOTIDE POLYMORPHISM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.
Fil: Perez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; Argentina
Fil: Barbar, Hanny. Universidad Abierta Interamericana; Argentina
Fil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.
publishDate 2023
dc.date.none.fl_str_mv 2023-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/220903
Perez Lloret, Santiago; Chevalier, Guenson; Bordet, Sofía; Barbar, Hanny; Capani, Francisco; et al.; The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease; MDPI; Brain Sciences; 13; 8; 8-2023; 1-14
2076-3425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/220903
identifier_str_mv Perez Lloret, Santiago; Chevalier, Guenson; Bordet, Sofía; Barbar, Hanny; Capani, Francisco; et al.; The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease; MDPI; Brain Sciences; 13; 8; 8-2023; 1-14
2076-3425
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci13081146
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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