Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset


Por: Billingsley K.J., Barbosa I.A., Bandrés-Ciga S., Quinn J.P., Bubb V.J., Deshpande C., Botia J.A., Reynolds R.H., Zhang D., Simpson M.A., Blauwendraat C., Gan-Or Z., Gibbs J.R., Nalls M.A., Singleton A., Noyce A., Tucci A., Middlehurst B., Kia D., Tan M., Houlden H., Morris H.R., Plun-Favreau H., Holmans P., Hardy J., Trabzuni D., Bras J., Mok K., Kinghorn K., Wood N., Lewis P., Guerreiro R., Lovering R., R’Bibo L., Rizig M., Escott-Price V., Chelban V., Foltynie T., Williams N., Brice A., Danjou F., Lesage S., Martinez M., Giri A., Schulte C., Brockmann K., Simón-Sánchez J., Heutink P., Rizzu P., Sharma M., Gasser T., Nicolas A., Cookson M., Faghri F., Hernandez D., Shulman J., Robak L., Lubbe S., Finkbeiner S., Mencacci N., Lungu C., Scholz S., Reed X., Leonard H., Rouleau G., Krohan L., van Hilten J., Marinus J., Adarmes-Gómez A., Aguilar M., Alvarez I., Alvarez V., Javier Barrero F., Bergareche Yarza J., Bernal-Bernal I., Blazquez M., Bernal M.B.-T., Boungiorno M., Buiza-Rueda D., Cámara A., Carcel M., Carrillo F., Carrión-Claro M., Cerdan D., Clarimón J., Compta Y., Diez-Fairen M., Dols-Icardo O., Duarte J., Duran R., Escamilla-Sevilla F., Ezquerra M., Fernández M., Fernández-Santiago R., Garcia C., García-Ruiz P., Gómez-Garre P., Heredia M.G., Gonzalez-Aramburu I., Pagola A.G., Hoenicka J., Infante J., Jesús S., Jimenez-Escrig A., Kulisevsky J., Labrador-Espinosa M., Lopez-Sendon J., de Munain Arregui A.L., Macias D., Torres I.M., Marín J., Marti M.J., Martínez-Castrillo J., Méndez-del-Barrio C., Menéndez González M., Mínguez A., Mir P., Rezola E.M., Muñoz E., Pagonabarraga J., Pastor P., Errazquin F.P., Periñán-Tocino T., Ruiz-Martínez J., Ruz C., Rodriguez A.S., Sierra M., Suarez-Sanmartin E., Tabernero C., Tartari J.P., Tejera-Parrado C., Tolosa E., Valldeoriola F., Vargas-González L., Vela L., Vives F., Zimprich A., Pihlstrom L., Taba P., Majamaa K., Siitonen A., Okubadejo N., Ojo O., Ryten M., Koks S.

Publicada: 1 ene 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. © 2019, The Author(s).

Filiaciones:
Billingsley K.J.:
 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, , University of Liverpool, Liverpool, United Kingdom

 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Barbosa I.A.:
 Department of Medical and Molecular Genetics, King’s College London School of Basic and Medical Biosciences, London, SE1 9RT, United Kingdom

Bandrés-Ciga S.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Quinn J.P.:
 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, , University of Liverpool, Liverpool, United Kingdom

Bubb V.J.:
 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, , University of Liverpool, Liverpool, United Kingdom

Deshpande C.:
 Clinical Genetics Unit, Guys and St. Thomas’ NHS Foundation Trust, London, SE1 9RT, United Kingdom

Botia J.A.:
 Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, Murcia, 30100, Spain

 Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, United Kingdom

Reynolds R.H.:
 Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, United Kingdom

Zhang D.:
 Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, United Kingdom

Simpson M.A.:
 Department of Medical and Molecular Genetics, King’s College London School of Basic and Medical Biosciences, London, SE1 9RT, United Kingdom

Blauwendraat C.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Gan-Or Z.:
 Montreal Neurological Institute, McGill University, Montréal, QC, Canada

 Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada

 Department of Human Genetics, McGill University, Montréal, QC, Canada

Gibbs J.R.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Nalls M.A.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

 Data Tecnica International, Glen Echo, MD 20812, United States

Singleton A.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Noyce A.:
 Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, QMUL, London, United Kingdom

Tucci A.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Middlehurst B.:
 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, , University of Liverpool, Liverpool, United Kingdom

Kia D.:
 UCL Genetics Institute

Tan M.:
 Department of Clinical Neuroscience, University College London, London, United Kingdom

 University College London, London, United Kingdom

Houlden H.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Morris H.R.:
 Department of Clinical Neuroscience, University College London, London, United Kingdom

 University College London, London, United Kingdom

Plun-Favreau H.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Holmans P.:
 Biostatistics & Bioinformatics Unit, Institute of Psychological Medicine and Clinical Neuroscience, MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff, United Kingdom

Hardy J.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Trabzuni D.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

 Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia

Bras J.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

 and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

 UK Dementia Research Institute at UCL and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Mok K.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Kinghorn K.:
 Institute of Healthy Ageing, University College London, London, United Kingdom

 University College London, London, United Kingdom

Wood N.:
 UCL Genetics Institute

Lewis P.:
 University of Reading, Reading, United Kingdom

Guerreiro R.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

 and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

 UK Dementia Research Institute at UCL and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Lovering R.:
 University College London, London, United Kingdom

R’Bibo L.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Rizig M.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Escott-Price V.:
 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom

 Cardiff University School of Medicine, Cardiff, United Kingdom

Chelban V.:
 Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Foltynie T.:
 Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, United Kingdom

Williams N.:
 Cardiff University School of Medicine, Cardiff, United Kingdom

Brice A.:
 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, Paris, France

Danjou F.:
 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, Paris, France

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, Paris, France

Martinez M.:
 INSERM UMR 1220

Giri A.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Schulte C.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Brockmann K.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Simón-Sánchez J.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Heutink P.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Rizzu P.:
 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Sharma M.:
 Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany

Gasser T.:
 Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

 DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

Nicolas A.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Cookson M.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Faghri F.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

 Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, United States

Hernandez D.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Shulman J.:
 Departments of Neurology, Neuroscience, and Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, United States

 Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United States

 Baylor College of Medicine, Houston, TX, United States

Robak L.:
 Baylor College of Medicine, Houston, TX, United States

Lubbe S.:
 Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

 Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Finkbeiner S.:
 Departments of Neurology and Physiology, University of California, San Francisco, CA, United States

 Gladstone Institute of Neurological Disease, San Francisco, CA, United States

 Taube/Koret Center for Neurodegenerative Disease Research, San Francisco, CA, United States

Mencacci N.:
 Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Lungu C.:
 National Institutes of Health Division of Clinical Research, NINDS, National Institutes of Health, Bethesda, MD, United States

Scholz S.:
 Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United States

Reed X.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Leonard H.:
 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States

Rouleau G.:
 Montreal Neurological Institute, McGill University, Montréal, QC, Canada

Krohan L.:
 Department of Human Genetics, McGill University, Montréal, QC H3A 0G4, Canada

van Hilten J.:
 Department of Neurology, Leiden University Medical Center, Leiden, Netherlands

Marinus J.:
 Department of Neurology, Leiden University Medical Center, Leiden, Netherlands

Adarmes-Gómez A.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Aguilar M.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Alvarez I.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Alvarez V.:
 Hospital Universitario Central de Asturias, Oviedo, Spain

Javier Barrero F.:
 Hospital Universitario Parque Tecnologico de la Salud, Granada, Spain

Bergareche Yarza J.:
 Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain

Bernal-Bernal I.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Blazquez M.:
 Hospital Universitario Central de Asturias, Oviedo, Spain

Bernal M.B.-T.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Boungiorno M.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Buiza-Rueda D.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Cámara A.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Carcel M.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Carrillo F.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Carrión-Claro M.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Cerdan D.:
 Hospital General de Segovia, Segovia, Spain

Clarimón J.:
 Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

Compta Y.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Diez-Fairen M.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Dols-Icardo O.:
 Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

Duarte J.:
 Hospital General de Segovia, Segovia, Spain

Duran R.:
 Centro de Investigacion Biomedica, Universidad de Granada, Granada, Spain

Escamilla-Sevilla F.:
 Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Granada, Spain

Ezquerra M.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Fernández M.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Fernández-Santiago R.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Garcia C.:
 Hospital Universitario Central de Asturias, Oviedo, Spain

García-Ruiz P.:
 Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain

Gómez-Garre P.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Heredia M.G.:
 Hospital Universitario Virgen de la Victoria, Málaga, Spain

Gonzalez-Aramburu I.:
 Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain

Pagola A.G.:
 Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain

Hoenicka J.:
 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

Infante J.:
 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

 Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain

Jesús S.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Jimenez-Escrig A.:
 Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain

Kulisevsky J.:
 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

 Movement Disorders Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

Labrador-Espinosa M.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Lopez-Sendon J.:
 Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain

de Munain Arregui A.L.:
 Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain

Macias D.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Torres I.M.:
 Department of Neurology, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Valencia, Spain

Marín J.:
 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

 Movement Disorders Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

Marti M.J.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Martínez-Castrillo J.:
 Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain

Méndez-del-Barrio C.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Menéndez González M.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Mínguez A.:
 Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Granada, Spain

Mir P.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Rezola E.M.:
 Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain

Muñoz E.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Pagonabarraga J.:
 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

 Movement Disorders Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

Pastor P.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Errazquin F.P.:
 Hospital Universitario Virgen de la Victoria, Málaga, Spain

Periñán-Tocino T.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Ruiz-Martínez J.:
 Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain

Ruz C.:
 Centro de Investigacion Biomedica, Universidad de Granada, Granada, Spain

Rodriguez A.S.:
 Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain

Sierra M.:
 Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain

Suarez-Sanmartin E.:
 Clinical Genetics Unit, Guys and St. Thomas’ NHS Foundation Trust, London, SE1 9RT, United Kingdom

Tabernero C.:
 Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain

Tartari J.P.:
 Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain

Tejera-Parrado C.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Tolosa E.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Valldeoriola F.:
 Hospital Clínic de Barcelona, Barcelona, Spain

Vargas-González L.:
 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Vela L.:
 Department of Neurology, Hospital Universitario Fundación Alcorcón, Madrid, Spain

Vives F.:
 Centro de Investigacion Biomedica, Universidad de Granada, Granada, Spain

Zimprich A.:
 Department of Neurology, Medical University of Vienna, Vienna, Austria

Pihlstrom L.:
 Department of Neurology, Oslo University Hospital, Oslo, Norway

Taba P.:
 Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia

Majamaa K.:
 Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland

 Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland

Siitonen A.:
 Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland

Okubadejo N.:
 University of Lagos, Yaba, Lagos State, Nigeria

Ojo O.:
 University of Lagos, Yaba, Lagos State, Nigeria

Ryten M.:
 Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, United Kingdom

Koks S.:
 The Perron Institute for Neurological and Translational Science, 8 Verdun Street, Nedlands, WA 6009, Australia

 Centre for Comparative Genomics, Murdoch University, Murdoch, 6150, Australia
ISSN: 23738057
Editorial
NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Alemania
Tipo de documento: Article
Volumen: 5 Número: 1
Páginas:
WOS Id: 000468982900001
ID de PubMed: 31123700
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