Artículo
New insights into the genetic etiology of Alzheimer?s disease and related dementias
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
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Fecha de publicación:
04/2022
Editorial:
Nature Publishing Group
Revista:
Nature Genetics
ISSN:
1061-4036
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Alzheimer’s disease
,
dementias
,
genetic
,
APOE
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Colecciones
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Citación
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
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