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(2022).
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Nature Genet., 54 (4).
S. 412 - 441.
BERLIN:
NATURE PORTFOLIO.
ISSN 1546-1718
Full text not available from this repository.
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 epsilon 4 allele. Meta-analysis of genome-wide association studies on Alzheimer's disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer's disease and dementia.
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Journal Article
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Bellenguez, Celine | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kucukali, Fahri | UNSPECIFIED | orcid.org/0000-0002-3835-9639 | UNSPECIFIED | Jansen, Iris E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kleineidam, Luca | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Moreno-Grau, Sonia | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Amin, Najaf | UNSPECIFIED | orcid.org/0000-0002-8944-1771 | UNSPECIFIED | Naj, Adam C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Campos-Martin, Rafael | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Grenier-Boley, Benjamin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Andrade, Victor | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Holmans, Peter A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Boland, Anne | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Damotte, Vincent | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van der Lee, Sven J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Costa, Marcos R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kuulasmaa, Teemu | UNSPECIFIED | UNSPECIFIED 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|
URN: |
urn:nbn:de:hbz:38-699726 |
DOI: |
10.1038/s41588-022-01024-z |
Journal or Publication Title: |
Nature Genet. |
Volume: |
54 |
Number: |
4 |
Page Range: |
S. 412 - 441 |
Date: |
2022 |
Publisher: |
NATURE PORTFOLIO |
Place of Publication: |
BERLIN |
ISSN: |
1546-1718 |
Language: |
English |
Faculty: |
Unspecified |
Divisions: |
Unspecified |
Subjects: |
no entry |
Uncontrolled Keywords: |
Keywords | Language |
---|
GENOME-WIDE ASSOCIATION; NECROSIS-FACTOR-ALPHA; RISK LOCI; PREDICTION MODELS; AMYLOID-BETA; METAANALYSIS; VARIANTS; GENERATION; IMPUTATION; RESPONSES | Multiple languages | Genetics & Heredity | Multiple languages |
|
URI: |
http://kups.ub.uni-koeln.de/id/eprint/69972 |
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