Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset
Billingsley, K. J. (National Institute on Aging (Estats Units d'Amèrica))
Barbosa, Ines (King's College London)
Bandres-Ciga, Sara ![Identificador ORCID](/img/uab/orcid.ico)
(National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Quinn, J. P.
Bubb, Vivien
Deshpande, Charulata (Clinical Genetics Unit. Guys and St. Thomas' NHS Foundation Trust)
Botia, J. A. (Department of Neurodegenerative Disease. UCL Institute of Neurology)
Reynolds, Regina H
(Department of Neurodegenerative Disease. UCL Institute of Neurology)
Zhang, D. (Department of Neurodegenerative Disease. UCL Institute of Neurology)
Simpson, M. A. (King's College London)
Blauwendraat, Cornelis (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Gan-Or, Z. (Department of Human Genetics. McGill University)
Gibbs, J. R. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Nalls, M. A. (Data Tecnica International)
Singleton, A. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Noyce, A. (Preventive Neurology Unit. Wolfson Institute of Preventive Medicine. QMUL)
Tucci, A. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Middlehurst, B.
Kia, Demis A (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Tan, M. (Department of Clinical Neuroscience. University College London)
Houlden, Henry
(UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Morris, H. R. (Department of Clinical Neuroscience. University College London)
Plun-Favreau, H. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Holmans, Peter
(MRC Centre for Neuropsychiatric Genetics & Genomics)
Hardy, J. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Trabzuni, D. (Department of Genetics. King Faisal Specialist Hospital and Research Centre)
Bras, Jose
(UCL Institute of Neurology (Regne Unit). UK Dementia Research Institute)
Mok, K. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Kinghorn, K. (Institute of Healthy Ageing. University College London)
Wood, N. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Lewis, P. (University of Reading)
Guerreiro, Rita
(UCL Institute of Neurology (Regne Unit). UK Dementia Research Institute)
Lovering, R. (University College London)
R'Bibo, L. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Rizig, M. (UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Escott-Price, Valentina
(Cardiff University School of Medicine)
Chelban, Viorica
(UCL Institute of Neurology (Regne Unit). Department of Molecular Neuroscience)
Foltynie, T. (Department of Neurodegenerative Disease. UCL Institute of Neurology)
Williams, Nigel (Cardiff University School of Medicine)
Brice, Alexis
(Institut du Cerveau et de la Moelle épinière. ICM. Inserm U 1127. CNRS. UMR 7225. Sorbonne Universités. UPMC University Paris 06. UMR S 1127. AP-HP. Pitié-Salpêtrière Hospital)
Danjou, Fabrice
(Institut du Cerveau et de la Moelle épinière. ICM. Inserm U 1127. CNRS. UMR 7225. Sorbonne Universités. UPMC University Paris 06. UMR S 1127. AP-HP. Pitié-Salpêtrière Hospital)
Lesage, S. (Institut du Cerveau et de la Moelle épinière. ICM. Inserm U 1127. CNRS. UMR 7225. Sorbonne Universités. UPMC University Paris 06. UMR S 1127. AP-HP. Pitié-Salpêtrière Hospital)
Martinez, M. (INSERM UMR 1220; and Paul Sabatier University)
Giri, A. (DZNE. German Center for Neurodegenerative Diseases)
Schulte, C. (DZNE. German Center for Neurodegenerative Diseases)
Brockmann, Kathrin
(DZNE. German Center for Neurodegenerative Diseases)
Simón-Sánchez, J. (DZNE. German Center for Neurodegenerative Diseases)
Heutink, Peter
(DZNE. German Center for Neurodegenerative Diseases)
Rizzu, P. (DZNE. German Center for Neurodegenerative Diseases)
Sharma, M. (Centre for Genetic Epidemiology. Institute for Clinical Epidemiology and Applied Biometry. University of Tubingen)
Gasser, Thomas
(DZNE. German Center for Neurodegenerative Diseases)
Nicolas, A. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Cookson, Mark R (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Faghri, Faraz (Department of Computer Science. University of Illinois at Urbana-Champaign)
Hernández, Dena (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Shulman, J. (Jan and Dan Duncan Neurological Research Institute. Texas Children's Hospital)
Robak, L. (Baylor College of Medicine)
Lubbe, S. (Ken and Ruth Davee Department of Neurology. Northwestern University Feinberg School of Medicine)
Finkbeiner, S. (Taube/Koret Center for Neurodegenerative Disease Research)
Mencacci, N. (Northwestern University Feinberg School of Medicine)
Lungu, C. (National Institutes of Health Division of Clinical Research. NINDS. National Institutes of Health)
Scholz, S. (Neurodegenerative Diseases Research Unit. National Institute of Neurological Disorders and Stroke)
Reed, X. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Leonard, H. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Rouleau, G. (Montreal Neurological Institute. McGill University)
Krohan, L. (Department of Human Genetics. McGill University)
van Hilten, J. (Department of Neurology. Leiden University Medical Center)
Marinus, J. (Department of Neurology. Leiden University Medical Center)
Adarmes-Gómez, A.D
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Aguilar Barberà, Miquel (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Alvarez, Ignacio
(Mútua de Terrassa)
Alvarez, Victoria
(Hospital Universitario Central de Asturias)
Javier Barrero, F. (Hospital Universitario Parque Tecnologico de la Salud)
Bergareche Yarza, J. (Biodonostia Osasun Ikerketako Institutura (País Basc))
Bernal-Bernal, I. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Blázquez Estrada, Marta
(Hospital Universitario Central de Asturias)
Bernal, M. B. T. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Boungiorno, M. T (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Buiza-Rueda, Dolores
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Cámara, Ana
(Hospital Clínic i Provincial de Barcelona)
Carcel, M. (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Carrillo, F. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Carrión-Claro, M. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Cerdan, Debora
(Hospital General de Segovia)
Clarimón, Jordi
(Institut d'Investigació Biomèdica Sant Pau)
Compta, Yaroslau
(Hospital Clínic i Provincial de Barcelona)
Diez-Fairen, Monica.
(Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Dols Icardo, Oriol
(Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Duarte, J. (Hospital General de Segovia)
Duran, Raquel (Centro de Investigacion Biomedica. Universidad de Granada)
Escamilla Sevilla, Francisco
(Instituto de Investigación Sanitaria de Granada)
Ezquerra, Mario
(Hospital Clínic i Provincial de Barcelona)
Fernández, M. (Hospital Clínic i Provincial de Barcelona)
Fernández-Santiago, Rubén
(Hospital Clínic i Provincial de Barcelona)
Garcia, C.. (Hospital Universitario Central de Asturias)
García-Ruiz, P. (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Gómez-Garre, Pilar
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Heredia, M. G. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Gonzalez-Aramburu, Isabel
(Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Gorostidi Pagola, Ana (Biodonostia Osasun Ikerketako Institutura (País Basc))
Hoenicka, J. (Institut de Recerca Sant Joan de Déu)
Infante, J. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Jesús, S. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Jiménez-Escrig, Adriano
(Hospital Universitario Ramón y Cajal (Madrid))
Kulisevsky, Jaime
(Institut d'Investigació Biomèdica Sant Pau)
Labrador-Espinosa, Miguel A
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Lopez-Sendon, J. (Hospital Universitario Ramón y Cajal (Madrid))
de Munain Arregui, A. L. (Hospital Universitario Ramón y Cajal (Madrid))
Macías-García, Daniel
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Torres, I. M. (Hospital Universitari i Politècnic La Fe (València))
Marín, J. (Institut d'Investigació Biomèdica Sant Pau)
Marti, M. J. (Hospital Clínic i Provincial de Barcelona)
Martínez-Castrillo, J. (Hospital Universitario Ramón y Cajal (Madrid))
Méndez-del-Barrio, C. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Menéndez González, M. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Mínguez, A. (Instituto de Investigación Sanitaria de Granada)
Mir, P. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Rezola, E. M. (Biodonostia Osasun Ikerketako Institutura (País Basc))
Muñoz García, José Esteban
(Hospital Clínic i Provincial de Barcelona)
Pagonabarraga Mora, Javier
(Institut d'Investigació Biomèdica Sant Pau)
Pastor, Pau
(Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Errazquin, F. P. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Periñán-Tocino, T. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ruiz-Martínez, J. (Biodonostia Osasun Ikerketako Institutura (País Basc))
Ruz, C. (Centro de Investigacion Biomedica. Universidad de Granada)
Rodriguez, A. S. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Sierra, M. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Suarez-Sanmartin, E. (Clinical Genetics Unit. Guys and St. Thomas' NHS Foundation Trust)
Tabernero, C. (Hospital Universitario Ramón y Cajal (Madrid))
Tartari, J. P. (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Tejera-Parrado, C. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Tolosa, E. (Hospital Clínic i Provincial de Barcelona)
Valldeoriola, F. (Hospital Clínic i Provincial de Barcelona)
Vargas-González, L. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Vela, Lydia
(Hospital Universitario Fundación Alcorcón)
Vives, Francisco (Centro de Investigacion Biomedica. Universidad de Granada)
Zimprich, Alexander (Department of Neurology. Medical University of Vienna)
Pihlstrom, L. (Oslo University Hospital (Oslo, Noruega))
Taba, Pille
(Department of Neurology and Neurosurgery. University of Tartu)
Majamaa, K. (Oulu University Hospital (Finlàndia))
Siitonen, A. (Institute of Clinical Medicine. Department of Neurology. University of Oulu)
Okubadejo, N. (University of Lagos)
Ojo, O. (University of Lagos)
Ryten, Mina (Department of Neurodegenerative Disease. UCL Institute of Neurology)
Koks, S. (Centre for Comparative Genomics. Murdoch University)
Universitat Autònoma de Barcelona
Fecha: |
2019 |
Resumen: |
Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson's disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial function-associated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD. |
Nota: |
Altres ajuts: This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project ZO1 AG000949. |
Derechos: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ![Creative Commons](/img/licenses/by.ico) |
Lengua: |
Anglès |
Documento: |
Article ; recerca ; Versió publicada |
Materia: |
Medical genetic ;
Risk factors |
Publicado en: |
NPJ Parkinson's disease, Vol. 5 Núm. 1 (january 2019) , p. 8, ISSN 2373-8057 |
DOI: 10.1038/s41531-019-0080-x
PMID: 31123700
El registro aparece en las colecciones:
Documentos de investigación >
Documentos de los grupos de investigación de la UAB >
Centros y grupos de investigación (producción científica) >
Ciencias de la salud y biociencias >
Institut de Recerca Sant PauArtículos >
Artículos de investigaciónArtículos >
Artículos publicados
Registro creado el 2020-06-03, última modificación el 2024-07-24