New insights into the genetic etiology of Alzheimer?s disease and related dementias
- Autores
- Bellenguez, Céline; Kucukali, Fahri; Jansen, Iris; Kleineidam, Lucas; Moreno Grau, Sonia; Morelli, Laura; Galeano, Pablo; Novack, Gisela Vanina; Prestia, Federico Ariel; Castaño, Eduardo Miguel; Ruiz, Agustín; Ramirez, Alfredo; Lambert, Jean Charles
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Bellenguez, Céline. Inserm; Francia. Université de Lille; Francia
Fil: Kucukali, Fahri. Center For Molecular Neurology; Bélgica. University of Antwerp; Bélgica
Fil: Jansen, Iris. Vrije Universiteit Amsterdam; Países Bajos
Fil: Kleineidam, Lucas. University Of Cologne; Alemania
Fil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Novack, Gisela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Prestia, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ruiz, Agustín. Universitat Internacional de Catalunya; España
Fil: Ramirez, Alfredo. University Of Cologne; Alemania
Fil: Lambert, Jean Charles. Inserm; Francia - Materia
-
Alzheimer’s disease
dementias
genetic
APOE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/218139
Ver los metadatos del registro completo
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New insights into the genetic etiology of Alzheimer?s disease and related dementiasBellenguez, CélineKucukali, FahriJansen, IrisKleineidam, LucasMoreno Grau, SoniaMorelli, LauraGaleano, PabloNovack, Gisela VaninaPrestia, Federico ArielCastaño, Eduardo MiguelRuiz, AgustínRamirez, AlfredoLambert, Jean CharlesAlzheimer’s diseasedementiasgeneticAPOEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Characterization 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.Fil: Bellenguez, Céline. Inserm; Francia. Université de Lille; FranciaFil: Kucukali, Fahri. Center For Molecular Neurology; Bélgica. University of Antwerp; BélgicaFil: Jansen, Iris. Vrije Universiteit Amsterdam; Países BajosFil: Kleineidam, Lucas. University Of Cologne; AlemaniaFil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; EspañaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Novack, Gisela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Prestia, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ruiz, Agustín. Universitat Internacional de Catalunya; EspañaFil: Ramirez, Alfredo. University Of Cologne; AlemaniaFil: Lambert, Jean Charles. Inserm; FranciaNature Publishing Group2022-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218139Bellenguez, Céline; Kucukali, Fahri; Jansen, Iris; Kleineidam, Lucas; Moreno Grau, Sonia; et al.; New insights into the genetic etiology of Alzheimer?s disease and related dementias; Nature Publishing Group; Nature Genetics; 54; 4-2022; 412-4361061-4036CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41588-022-01024-zinfo:eu-repo/semantics/altIdentifier/url/https://doi.org/10.1038/s41588-022-01024-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:43Zoai:ri.conicet.gov.ar:11336/218139instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:42:43.505CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
title |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
spellingShingle |
New insights into the genetic etiology of Alzheimer?s disease and related dementias Bellenguez, Céline Alzheimer’s disease dementias genetic APOE |
title_short |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
title_full |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
title_fullStr |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
title_full_unstemmed |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
title_sort |
New insights into the genetic etiology of Alzheimer?s disease and related dementias |
dc.creator.none.fl_str_mv |
Bellenguez, Céline Kucukali, Fahri Jansen, Iris Kleineidam, Lucas Moreno Grau, Sonia Morelli, Laura Galeano, Pablo Novack, Gisela Vanina Prestia, Federico Ariel Castaño, Eduardo Miguel Ruiz, Agustín Ramirez, Alfredo Lambert, Jean Charles |
author |
Bellenguez, Céline |
author_facet |
Bellenguez, Céline Kucukali, Fahri Jansen, Iris Kleineidam, Lucas Moreno Grau, Sonia Morelli, Laura Galeano, Pablo Novack, Gisela Vanina Prestia, Federico Ariel Castaño, Eduardo Miguel Ruiz, Agustín Ramirez, Alfredo Lambert, Jean Charles |
author_role |
author |
author2 |
Kucukali, Fahri Jansen, Iris Kleineidam, Lucas Moreno Grau, Sonia Morelli, Laura Galeano, Pablo Novack, Gisela Vanina Prestia, Federico Ariel Castaño, Eduardo Miguel Ruiz, Agustín Ramirez, Alfredo Lambert, Jean Charles |
author2_role |
author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Alzheimer’s disease dementias genetic APOE |
topic |
Alzheimer’s disease dementias genetic APOE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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. Fil: Bellenguez, Céline. Inserm; Francia. Université de Lille; Francia Fil: Kucukali, Fahri. Center For Molecular Neurology; Bélgica. University of Antwerp; Bélgica Fil: Jansen, Iris. Vrije Universiteit Amsterdam; Países Bajos Fil: Kleineidam, Lucas. University Of Cologne; Alemania Fil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Novack, Gisela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Prestia, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Ruiz, Agustín. Universitat Internacional de Catalunya; España Fil: Ramirez, Alfredo. University Of Cologne; Alemania Fil: Lambert, Jean Charles. Inserm; Francia |
description |
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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/218139 Bellenguez, Céline; Kucukali, Fahri; Jansen, Iris; Kleineidam, Lucas; Moreno Grau, Sonia; et al.; New insights into the genetic etiology of Alzheimer?s disease and related dementias; Nature Publishing Group; Nature Genetics; 54; 4-2022; 412-436 1061-4036 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/218139 |
identifier_str_mv |
Bellenguez, Céline; Kucukali, Fahri; Jansen, Iris; Kleineidam, Lucas; Moreno Grau, Sonia; et al.; New insights into the genetic etiology of Alzheimer?s disease and related dementias; Nature Publishing Group; Nature Genetics; 54; 4-2022; 412-436 1061-4036 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41588-022-01024-z info:eu-repo/semantics/altIdentifier/url/https://doi.org/10.1038/s41588-022-01024-z |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |