SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease
Q1
- Autores:
-
Fernández-Santiago, Rubén
Martín-Flores, Núria
Antonelli, Francesca
Cerquera, Catalina
Moreno, Verónica
Bandres-Ciga, Sara
Manduchi, Elisabetta
Tolosa, Eduard
Singleton, Andrew B.
Moore, Jason H.
The International Parkinson’s Disease Genomics Consortium
Martí, María-Josep
Ezquerra, Mario
Malagelada, Cristina
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2019
- Institución:
- Pontificia Universidad Javeriana
- Repositorio:
- Repositorio Universidad Javeriana
- Idioma:
- eng
- OAI Identifier:
- oai:repository.javeriana.edu.co:10554/60288
- Acceso en línea:
- https://login.ezproxy.javeriana.edu.co/login?url=https://search.ebscohost.com/login.aspx?direct=true&AuthType=ip&db=edselc&AN=edselc.2-52.0-85068083474&lang=es&site=eds-live
http://hdl.handle.net/10554/60288
https://doi.org/10.1002/mds.27770
- Palabra clave:
- Age at onset
Alpha-synuclein
Epistasis
mTOR
Parkinson’s disease
SNP
- Rights
- License
- Atribución-NoComercial 4.0 Internacional
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| dc.title.spa.fl_str_mv |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| title |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| spellingShingle |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease Age at onset Alpha-synuclein Epistasis mTOR Parkinson’s disease SNP |
| title_short |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| title_full |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| title_fullStr |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| title_full_unstemmed |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| title_sort |
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease |
| dc.creator.fl_str_mv |
Fernández-Santiago, Rubén Martín-Flores, Núria Antonelli, Francesca Cerquera, Catalina Moreno, Verónica Bandres-Ciga, Sara Manduchi, Elisabetta Tolosa, Eduard Singleton, Andrew B. Moore, Jason H. The International Parkinson’s Disease Genomics Consortium Martí, María-Josep Ezquerra, Mario Malagelada, Cristina |
| dc.contributor.author.none.fl_str_mv |
Fernández-Santiago, Rubén Martín-Flores, Núria Antonelli, Francesca Cerquera, Catalina Moreno, Verónica Bandres-Ciga, Sara Manduchi, Elisabetta Tolosa, Eduard Singleton, Andrew B. Moore, Jason H. The International Parkinson’s Disease Genomics Consortium Martí, María-Josep Ezquerra, Mario Malagelada, Cristina |
| dc.contributor.corporatename.spa.fl_str_mv |
Pontificia Universidad Javeriana. Facultad de Medicina. Departamento de Neurociencias. Neurología Pontificia Universidad Javeriana. Facultad de Medicina. Hospital Universitario San Ignacio |
| dc.subject.keyword.spa.fl_str_mv |
Age at onset Alpha-synuclein Epistasis mTOR Parkinson’s disease SNP |
| topic |
Age at onset Alpha-synuclein Epistasis mTOR Parkinson’s disease SNP |
| description |
Q1 |
| publishDate |
2019 |
| dc.date.created.none.fl_str_mv |
2019-06 |
| dc.date.accessioned.none.fl_str_mv |
2022-06-14T16:22:37Z |
| dc.date.available.none.fl_str_mv |
2022-06-14T16:22:37Z |
| dc.type.local.spa.fl_str_mv |
Artículo de revista |
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http://purl.org/coar/resource_type/c_6501 |
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http://purl.org/coar/resource_type/c_6501 |
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| dc.identifier.issn.spa.fl_str_mv |
1531-8257 |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10554/60288 |
| dc.identifier.doi.spa.fl_str_mv |
https://doi.org/10.1002/mds.27770 |
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instname:Pontificia Universidad Javeriana |
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reponame:Repositorio Institucional - Pontificia Universidad Javeriana |
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| dc.language.iso.spa.fl_str_mv |
eng |
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eng |
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1 |
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22 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Movement Disorders |
| dc.relation.citationvolume.spa.fl_str_mv |
34 |
| dc.relation.citationissue.spa.fl_str_mv |
9 |
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Atribución-NoComercial 4.0 Internacional |
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http://creativecommons.org/licenses/by-nc/4.0/ |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/http://purl.org/coar/access_right/c_abf2Fernández-Santiago, RubénMartín-Flores, NúriaAntonelli, FrancescaCerquera, CatalinaMoreno, VerónicaBandres-Ciga, SaraManduchi, ElisabettaTolosa, EduardSingleton, Andrew B.Moore, Jason H.The International Parkinson’s Disease Genomics ConsortiumMartí, María-JosepEzquerra, MarioMalagelada, CristinaPontificia Universidad Javeriana. Facultad de Medicina. Departamento de Neurociencias. NeurologíaPontificia Universidad Javeriana. Facultad de Medicina. Hospital Universitario San Ignacio2022-06-14T16:22:37Z2022-06-14T16:22:37Z2019-06https://login.ezproxy.javeriana.edu.co/login?url=https://search.ebscohost.com/login.aspx?direct=true&AuthType=ip&db=edselc&AN=edselc.2-52.0-85068083474&lang=es&site=eds-live1531-8257http://hdl.handle.net/10554/60288https://doi.org/10.1002/mds.27770instname:Pontificia Universidad Javerianareponame:Repositorio Institucional - Pontificia Universidad Javerianarepourl:https://repository.javeriana.edu.coPDFapplication/pdfengSNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s DiseaseArtículo de revistahttp://purl.org/coar/resource_type/c_6501Q1Q1Background—Single nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson’s disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored. Objectives—The mechanistic target of rapamycin (mTOR) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO. Methods—Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson’s Disease Genomics Consortium. Results—In the discovery series cohort, we found a 4-loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P < .001). In addition, we also found a 3-loci epistatic combination of RPTOR rs11868112 and RPS6KA2 rs6456121 with SNCA rs356219, which was associated (odds ratio = 2.89; P < .0001) with differential AAO. The latter was further validated (odds ratio = 1.56; P = 0.046–0.047) in the International Parkinson’s Disease Genomics Consortium cohort. Conclusions—These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease.Revista Internacional - IndexadaSiAge at onsetAlpha-synucleinEpistasismTORParkinson’s diseaseSNP122Movement Disorders349ORIGINALa3734.pdfa3734.pdfArtículoapplication/pdf372108http://repository.javeriana.edu.co/bitstream/10554/60288/1/a3734.pdf2ce9ebadcbb495024841dc8acd8f7effMD51embargoed access|||9999-01-01LICENSElicense.txtlicense.txttext/plain; charset=utf-82603http://repository.javeriana.edu.co/bitstream/10554/60288/2/license.txt2070d280cc89439d983d9eee1b17df53MD52open accessTHUMBNAILa3734.pdf.jpga3734.pdf.jpgIM Thumbnailimage/jpeg10107http://repository.javeriana.edu.co/bitstream/10554/60288/3/a3734.pdf.jpg98c460bb8879407587f006237585dd80MD53open access10554/60288oai:repository.javeriana.edu.co:10554/602882022-06-15 03:06:35.671Repositorio Institucional - Pontificia Universidad Javerianarepositorio@javeriana.edu.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 |