Your browser doesn't support javascript.
loading
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E; Pedersen, Nancy L; Stringa, Najada; Zettergren, Anna; Hernández, Isabel; Montrreal, Laura; Antúnez, Carmen; Antonell, Anna; Tankard, Rick M; Bis, Joshua C; Sims, Rebecca; Bellenguez, Céline; Quintela, Inés; González-Perez, Antonio; Calero, Miguel; Franco-Macías, Emilio; Macías, Juan; Blesa, Rafael; Cervera-Carles, Laura; Menéndez-González, Manuel; Frank-García, Ana; Royo, Jose Luís; Moreno, Fermin; Huerto Vilas, Raquel; Baquero, Miquel; Diez-Fairen, Mónica; Lage, Carmen; García-Madrona, Sebastián; García-González, Pablo; Alarcón-Martín, Emilio; Valero, Sergi; Sotolongo-Grau, Oscar; Ullgren, Abbe; Naj, Adam C; Lemstra, Afina W; Benaque, Alba; Pérez-Cordón, Alba; Benussi, Alberto; Rábano, Alberto; Padovani, Alessandro; Squassina, Alessio; de Mendonça, Alexandre; Arias Pastor, Alfonso; Kok, Almar A L; Meggy, Alun.
Afiliação
  • de Rojas I; Research Center and Memory clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Moreno-Grau S; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Tesi N; Research Center and Memory clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Grenier-Boley B; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Andrade V; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
  • Jansen IE; Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
  • Pedersen NL; Delft Bioinformatics Lab, Delft Univeristy of Technology, Delft, The Netherlands.
  • Stringa N; Univ. Lille, Inserm, Institut Pasteur de Lille, CHU Lille, U1167-Labex DISTALZ-RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
  • Zettergren A; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
  • Hernández I; Department of Neurodegenerative diseases and Geriatric Psychiatry, University Clinic Bonn, Bonn, Germany.
  • Montrreal L; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
  • Antúnez C; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
  • Antonell A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Tankard RM; Amsterdam UMC-Vrije Universiteit Amsterdam, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
  • Bis JC; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap), University of Gothenburg, Gothenburg, Sweden.
  • Sims R; Research Center and Memory clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Bellenguez C; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Quintela I; Research Center and Memory clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • González-Perez A; Unidad de Demencias, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Calero M; Alzheimer's disease and other cognitive disorders unit. Service of Neurology, Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
  • Franco-Macías E; Mathematics and Statistics, Murdoch University, Perth, WA, Australia.
  • Macías J; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Blesa R; Division of Psychological Medicine and Clinial Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
  • Cervera-Carles L; Univ. Lille, Inserm, Institut Pasteur de Lille, CHU Lille, U1167-Labex DISTALZ-RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.
  • Menéndez-González M; Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3-ISCIII), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Frank-García A; CAEBI, Centro Andaluz de Estudios Bioinformáticos, Sevilla, Spain.
  • Royo JL; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Moreno F; UFIEC, Instituto de Salud Carlos III, Madrid, Spain.
  • Huerto Vilas R; CIEN Foundation/Queen Sofia Foundation Alzheimer Center, Madrid, Spain.
  • Baquero M; Unidad de Demencias, Servicio de Neurología y Neurofisiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
  • Diez-Fairen M; Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain.
  • Lage C; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • García-Madrona S; Department of Neurology, II B Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • García-González P; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Alarcón-Martín E; Department of Neurology, II B Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Valero S; Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Sotolongo-Grau O; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
  • Ullgren A; Departamento de Medicina, Universidad de Oviedo, Oviedo, Spain.
  • Naj AC; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Lemstra AW; Department of Neurology, La Paz University Hospital, Instituto de Investigación Sanitaria del Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
  • Benaque A; Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain.
  • Pérez-Cordón A; Universidad Autónoma de Madrid, Madrid, Spain.
  • Benussi A; Departamento de Especialidades Quirúrgicas, Bioquímicas e Inmunología, School of Medicine, University of Málaga, Málaga, Spain.
  • Rábano A; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Padovani A; Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain.
  • Squassina A; Neurosciences Area, Instituto Biodonostia, San Sebastian, Spain.
  • de Mendonça A; Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.
  • Arias Pastor A; Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain.
  • Kok AAL; Servei de Neurologia, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
  • Meggy A; Fundació Docència i Recerca MútuaTerrassa, Terrassa, Barcelona, Spain.
Nat Commun ; 12(1): 3417, 2021 06 07.
Article em En | MEDLINE | ID: mdl-34099642
ABSTRACT
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Herança Multifatorial / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Herança Multifatorial / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article