New insights into the genetic etiology of Alzheimer’s disease and related dementias
Entity
UAM. Departamento de Biología MolecularPublisher
Nature Publishing GroupDate
2022-04-04Citation
10.1038/s41588-022-01024-z
Nature Genetics 54.4 (2022): 412-436
ISSN
1061-4036DOI
10.1038/s41588-022-01024-zFunded by
This research was conducted using the UKBB resource (application number 61054). This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Note.Subjects
Alzheimer Disease; Genetic Predisposition to Disease; Biología y Biomedicina / BiologíaNote
Artículo escrito por un elevado número de autores, solo se referencia el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMRights
© 2022.The Author(s)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
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Google Scholar:Bellenguez, Céline
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Bullido Gómez-Heras, María Jesús
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