Your browser doesn't support javascript.
loading
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Bellenguez, Céline; Küçükali, Fahri; Jansen, Iris E; Kleineidam, Luca; Moreno-Grau, Sonia; Amin, Najaf; Naj, Adam C; Campos-Martin, Rafael; Grenier-Boley, Benjamin; Andrade, Victor; Holmans, Peter A; Boland, Anne; Damotte, Vincent; van der Lee, Sven J; Costa, Marcos R; Kuulasmaa, Teemu; Yang, Qiong; de Rojas, Itziar; Bis, Joshua C; Yaqub, Amber; Prokic, Ivana; Chapuis, Julien; Ahmad, Shahzad; Giedraitis, Vilmantas; Aarsland, Dag; Garcia-Gonzalez, Pablo; Abdelnour, Carla; Alarcón-Martín, Emilio; Alcolea, Daniel; Alegret, Montserrat; Alvarez, Ignacio; Álvarez, Victoria; Armstrong, Nicola J; Tsolaki, Anthoula; Antúnez, Carmen; Appollonio, Ildebrando; Arcaro, Marina; Archetti, Silvana; Pastor, Alfonso Arias; Arosio, Beatrice; Athanasiu, Lavinia; Bailly, Henri; Banaj, Nerisa; Baquero, Miquel; Barral, Sandra; Beiser, Alexa; Pastor, Ana Belén; Below, Jennifer E; Benchek, Penelope; Benussi, Luisa.
Afiliação
  • Bellenguez C; Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France. celine.bellenguez@pasteur-lille.fr.
  • Küçükali F; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
  • Jansen IE; Laboratory of Neurogenetics, Institute Born - Bunge, Antwerp, Belgium.
  • Kleineidam L; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
  • Moreno-Grau S; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
  • Amin N; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije University, Amsterdam, the Netherlands.
  • Naj AC; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • Campos-Martin R; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
  • Grenier-Boley B; German Center for Neurodegenerative Diseases (DZNE Bonn), Bonn, Germany.
  • Andrade V; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Holmans PA; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Boland A; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
  • Damotte V; Nuffield Department of Population Health, Oxford University, Oxford, UK.
  • van der Lee SJ; Department of Biostatistics, Epidemiology, and Informatics, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Costa MR; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Kuulasmaa T; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
  • Yang Q; Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
  • de Rojas I; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • Bis JC; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
  • Yaqub A; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.
  • Prokic I; CEA, Centre National de Recherche en Génomique Humaine, Université Paris-Saclay, Evry, France.
  • Chapuis J; Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
  • Ahmad S; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
  • Giedraitis V; Section Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
  • Aarsland D; Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
  • Garcia-Gonzalez P; Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
  • Abdelnour C; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
  • Alarcón-Martín E; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Alcolea D; Framingham Heart Study, Framingham, MA, USA.
  • Alegret M; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Alvarez I; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Álvarez V; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Armstrong NJ; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
  • Tsolaki A; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
  • Antúnez C; Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
  • Appollonio I; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
  • Arcaro M; LACDR, Leiden, the Netherlands.
  • Archetti S; Department of Public Health and Carins Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
  • Pastor AA; Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
  • Arosio B; Institute of Psychiatry, Psychology & Neuroscience, London, UK.
  • Athanasiu L; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Bailly H; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Banaj N; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Baquero M; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Barral S; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Beiser A; Department of Surgery, Biochemistry and Molecular Biology, School of Medicine, University of Málaga, Málaga, Spain.
  • Pastor AB; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
  • Below JE; Department of Neurology, II B Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Benchek P; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
  • Benussi L; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
Nat Genet ; 54(4): 412-436, 2022 04.
Article em En | MEDLINE | ID: mdl-35379992
ABSTRACT
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
Assuntos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: França