Moving beyond neurons : the role of cell type-specific gene regulation in Parkinson's disease heritability
Reynolds, Regina H (Department of Neurodegenerative Disease. University College London (UCL) Institute of Neurology)
Botía, Juan A. (Universidad de Murcia)
Nalls, Mike A. (Data Tecnica International (Maryland, Estats Units))
Noyce, Alastair J. (Preventive Neurology Unit. Wolfson Institute of Preventive Medicine. QMUL)
Nicolas, Aude (National Institute on Aging (Estats Units d'Amèrica))
Cookson, Mark R. (National Institute on Aging (Estats Units d'Amèrica))
Bandres-Ciga, Sara (National Institute on Aging (Estats Units d'Amèrica))
Gibbs, J. Raphael (National Institute on Aging (Estats Units d'Amèrica))
Hernandez, Dena G. (National Institute on Aging (Estats Units d'Amèrica))
Singleton, Andrew B. (National Institute on Aging (Estats Units d'Amèrica))
Reed, Xylena (National Institute on Aging (Estats Units d'Amèrica))
Leonard, Hampton (National Institute on Aging (Estats Units d'Amèrica))
Blauwendraat, Cornelis (National Institute of Neurological Disorders and Stroke)
Faghri, Faraz (Department of Computer Science. University of Illinois at Urbana-Champaign)
Bras, Jose (Department of Molecular Neuroscience. UCL)
Guerreiro, Rita (Department of Molecular Neuroscience. UCL)
Tucci, Arianna (Department of Molecular Neuroscience. UCL)
Kia, Demis A. (Department of Molecular Neuroscience. UCL)
Houlden, Henry (Department of Molecular Neuroscience. UCL)
Plun-Favreau, Helen (Department of Molecular Neuroscience. UCL)
Mok, Kin Ying (Department of Molecular Neuroscience. UCL)
Wood, Nicholas W. (Department of Molecular Neuroscience. UCL)
Lovering, Ruth Caroline (Department of Molecular Neuroscience. UCL)
R'Bibo, Lea (Department of Molecular Neuroscience. UCL)
Rizig, Mie (Department of Molecular Neuroscience. UCL)
Chelban, Viorica (Department of Molecular Neuroscience. UCL)
Trabzuni, Daniah (Department of Genetics. King Faisal Specialist Hospital and Research Centre)
Tan, Manuela (Department of Clinical Neuroscience. University College London)
Morris, Huw (Department of Clinical Neuroscience. University College London)
Middlehurst, Ben (Institute of Translational Medicine. University of Liverpool)
Quinn, John (Institute of Translational Medicine. University of Liverpool)
Billingsley, Kimberley (Institute of Translational Medicine. University of Liverpool)
Holmans, Peter (MRC Centre for Neuropsychiatric Genetics & Genomics)
Kinghorn, Kerri J. (Institute of Healthy Ageing. University College London)
Lewis, Patrick (University of Reading)
Escott-Price, Valentina (MRC Centre for Neuropsychiatric Genetics and Genomics. Cardiff University School of Medicine)
Williams, Nigel (MRC Centre for Neuropsychiatric Genetics and Genomics. Cardiff University School of Medicine)
Foltynie, Thomas (UCL Institute of Neurology (Regne Unit))
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, Suzanne (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)
Corvol, Jean-Christophe (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, Maria (Paul Sabatier University)
Giri, Anamika (DZNE. German Center for Neurodegenerative Diseases)
Schulte, Claudia (DZNE. German Center for Neurodegenerative Diseases)
Brockmann, Kathrin (DZNE. German Center for Neurodegenerative Diseases)
Simón-Sánchez, Javier (DZNE. German Center for Neurodegenerative Diseases)
Heutink, Peter (DZNE. German Center for Neurodegenerative Diseases)
Gasser, Thomas (DZNE. German Center for Neurodegenerative Diseases)
Rizzu, Patrizia (DZNE. German Center for Neurodegenerative Diseases)
Sharma, Manu (Centre for Genetic Epidemiology. Institute for Clinical Epidemiology and Applied Biometry. University of Tubingen)
Shulman, Joshua M. (Jan and Dan Duncan Neurological Research Institute. Texas Children's Hospital)
Robak, Laurie (Departments of Neurology. Neuroscience. and Molecular & Human Genetics. Baylor College of Medicine)
Lubbe, Steven (Ken and Ruth Davee Department of Neurology. Northwestern University Feinberg School of Medicine)
Mencacci, Niccolò Emanuele (Northwestern University Feinberg School of Medicine)
Finkbeiner, Steven (Gladstone Institute of Neurological Disease. Taube/Koret Center for Neurodegenerative Disease Research)
Lungu, Codrin (National Institutes of Health Division of Clinical Research. NINDS. National Institutes of Health)
Scholz, Sonja (Neurodegenerative Diseases Research Unit. National Institute of Neurological Disorders and Stroke)
Gan-Or, Ziv (Montreal Neurological Institute and Hospital. Departments of Neurology and Neurosurgery. Department of Human Genetics. McGill University)
Rouleau, Guy A.
Krohan, Lynne (Department of Human Genetics. McGill University)
van Hilten, Jacobus J. (Department of Neurology. Leiden University Medical Center)
Marinus, Johan (Department of Neurology. Leiden University Medical Center)
Adarmes-Gómez, A.D (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Bernal-Bernal, Inmaculada (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Bonilla-Toribio, Marta (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Buiza-Rueda, Dolores (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Carrillo, Fátima (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Carrión-Claro, Mario (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Mir, Pablo (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Gómez-Garre, Pilar (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Jesús, Silvia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Labrador-Espinosa, Miguel A. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Macías-García, Daniel (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Vargas-González, Laura (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Méndez-del-Barrio, Carlota (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Periñán-Tocino, Teresa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Tejera-Parrado, Cristina (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Diez-Fairen, Monica. (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Aguilar Barberà, Miquel (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Alvarez, Ignacio (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Boungiorno, Maria Teresa (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Carcel, Maria (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Pastor, Pau (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Tartari, Juan Pablo (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Alvarez, Victoria (Hospital Universitario Central de Asturias)
González, Manel Menéndez (Hospital Universitario Central de Asturias)
Blázquez Estrada, Marta (Hospital Universitario Central de Asturias)
Garcia, Ciara (Hospital Universitario Central de Asturias)
Suarez-Sanmartin, Esther (Hospital Universitario Central de Asturias)
Barrero, Francisco Javier (Hospital Universitario Parque Tecnologico de la Salud)
Rezola, Elisabet Mondragon (Biodonostia Osasun Ikerketako Institutura (País Basc))
Yarza, Jesús Alberto Bergareche (Biodonostia Osasun Ikerketako Institutura (País Basc))
Pagola, Ana Gorostidi (Biodonostia Osasun Ikerketako Institutura (País Basc))
de Munain Arregui, Adolfo López (Biodonostia Osasun Ikerketako Institutura (País Basc))
Ruiz-Martínez, J. (Biodonostia Osasun Ikerketako Institutura (País Basc))
Cerdan, Debora (Hospital General de Segovia)
Duarte, J. (Hospital General de Segovia)
Clarimón, Jordi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Dols Icardo, Oriol (Institut d'Investigació Biomèdica Sant Pau)
Infante, J. (University of Cantabria)
Marín, J. (Institut d'Investigació Biomèdica Sant Pau)
Kulisevsky, Jaime (Institut d'Investigació Biomèdica Sant Pau)
Pagonabarraga Mora, Javier (Institut d'Investigació Biomèdica Sant Pau)
Gonzalez-Aramburu, Isabel (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Rodriguez, A. S. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Sierra, M. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Duran, Raquel (Centro de Investigacion Biomedica. Universidad de Granada)
Ruz, C. (Centro de Investigacion Biomedica. Universidad de Granada)
Vives, F. (Centro de Investigacion Biomedica. Universidad de Granada)
Escamilla-Sevilla, F. (Instituto de Investigación Sanitaria de Granada)
Mínguez, A. (Instituto de Investigación Sanitaria de Granada)
Cámara, Ana (Hospital Clínic i Provincial de Barcelona)
Compta, Yaroslau (Hospital Clínic i Provincial de Barcelona)
Ezquerra, Mario (Hospital Clínic i Provincial de Barcelona)
Marti, M. J. (Hospital Clínic i Provincial de Barcelona)
Fernández, M. (Hospital Clínic i Provincial de Barcelona)
Muñoz García, José Esteban (Hospital Clínic i Provincial de Barcelona)
Fernández Santiago, Rubén (Hospital Clínic i Provincial de Barcelona)
Tolosa, E. (Hospital Clínic i Provincial de Barcelona)
Valldeoriola, F. (Hospital Clínic i Provincial de Barcelona)
García-Ruiz, P. (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Heredia, M. J. G. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Errazquin, F. P. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Hoenicka, J. (Institut de Recerca Sant Joan de Déu)
Jiménez-Escrig, Adriano (Hospital Universitario Ramón y Cajal (Madrid))
Martínez-Castrillo, J. C. (Hospital Universitario Ramón y Cajal (Madrid))
Lopez-Sendon, J. L. (Hospital Universitario Ramón y Cajal (Madrid))
Torres, I. M. (Hospital Universitari i Politècnic La Fe (València))
Tabernero, C. (Hospital General de Segovia)
Vela, Lydia (Hospital Universitario Fundación Alcorcón)
Zimprich, Alexander (Department of Neurology. Medical University of Vienna)
Pihlstrom, L. (Oslo University Hospital (Oslo, Noruega))
Koks, S. (Perron Institute for Neurological and Translational Science)
Taba, P. (Departments of Neurology and Neurosurgery. University of Tartu)
Majamaa, K. (Oulu University Hospital (Finlàndia))
Siitonen, A. (Oulu University Hospital (Finlàndia))
Okubadejo, N. U. (University of Lagos)
Ojo, O. O. (University of Lagos)
Pitcher, T. (Department of Medicine. University of Otago)
Anderson, T. (Department of Medicine. University of Otago)
Bentley, S. (Griffith Institute for Drug Discovery. Griffith University)
Fowdar, J. (Griffith Institute for Drug Discovery. Griffith University)
Mellick, G. (Griffith Institute for Drug Discovery. Griffith University)
Dalrymple-Alford, J. (Department Psychology. University of Canterbury. New Zealand Brain Research Institute)
Henders, Anjali K (Institute for Molecular Bioscience. University of Queensland)
Kassam, I. (Institute for Molecular Bioscience. University of Queensland)
Montgomery, G. (Institute for Molecular Bioscience. University of Queensland)
Sidorenko, J. (Institute for Molecular Bioscience. University of Queensland)
Zhang, F. (Institute for Molecular Bioscience. University of Queensland)
Xue, A. (Institute for Molecular Bioscience. University of Queensland)
Vallerga, C. L. (Institute for Molecular Bioscience. University of Queensland)
Wallace, Leanne (Institute for Molecular Bioscience. University of Queensland)
Wray, N. R. (Queensland Brain Institute. University of Queensland)
Yang, J. (Queensland Brain Institute. University of Queensland)
Visscher, P. M. (Queensland Brain Institute. University of Queensland)
Gratten, J. (Queensland Brain Institute. University of Queensland)
Silburn, P. A. (Queensland Brain Institute. University of Queensland)
Halliday, G. (University of Sydney. Brain and Mind Centre)
Hickie, Ian B (University of Sydney. Brain and Mind Centre)
Kwok, J. (University of Sydney. Brain and Mind Centre)
Lewis, S. (University of Sydney. Brain and Mind Centre)
Kennedy, M. (Department of Pathology. University of Otago)
Pearson, J. (Department of Pathology. University of Otago)
Hardy, J. (UK Dementia Research Institute at University College London (UCL))
Gagliano Taliun, Sarah A (Center for Statistical Genetics and Department of Biostatistics. University of Michigan)
Ryten, Mina (Department of Neurodegenerative Disease. University College London (UCL) Institute of Neurology)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	NPJ Parkinson's disease, Vol. 5 Núm. 1 (january 2019) , p. 6, ISSN 2373-8057

DOI: 10.1038/s41531-019-0076-6
PMID: 31016231

14 p, 2.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles