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dc.contributor.author |
Ghanbari, Mohsen |
|
dc.contributor.author |
Raj, Towfique |
|
dc.contributor.author |
Sachdev, Perminder |
|
dc.contributor.author |
Mather, Karen |
|
dc.contributor.author |
Jessen, Frank |
|
dc.contributor.author |
Ikram, M Arfan |
|
dc.contributor.author |
de Mendonça, Alexandre |
|
dc.contributor.author |
Hort, Jakub |
|
dc.contributor.author |
Tsolaki, Magda |
|
dc.contributor.author |
Pericak-Vance, Margaret A |
|
dc.contributor.author |
Amouyel, Philippe |
|
dc.contributor.author |
Williams, Julie |
|
dc.contributor.author |
Frikke-Schmidt, Ruth |
|
dc.contributor.author |
Clarimon, Jordi |
|
dc.contributor.author |
Deleuze, Jean-François |
|
dc.contributor.author |
Rossi, Giacomina |
|
dc.contributor.author |
Seshadri, Sudha |
|
dc.contributor.author |
Andreassen, Ole A |
|
dc.contributor.author |
Ingelsson, Martin |
|
dc.contributor.author |
Hiltunen, Mikko |
|
dc.contributor.author |
Sleegers, Kristel |
|
dc.contributor.author |
Schellenberg, Gerard D |
|
dc.contributor.author |
van Duijn, Cornelia M |
|
dc.contributor.author |
Sims, Rebecca |
|
dc.contributor.author |
van der Flier, Wiesje M |
|
dc.contributor.author |
Ruiz, Agustín |
|
dc.contributor.author |
Ramirez, Alfredo |
|
dc.contributor.author |
Lambert, Jean-Charles |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2022-08-22T03:34:32Z |
|
dc.date.available |
2022-08-22T03:34:32Z |
|
dc.date.issued |
2022-04-04 |
|
dc.identifier.citation |
(2022). Nature Genetics, 54(4), 412-436. |
|
dc.identifier.issn |
1061-4036 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/60887 |
|
dc.description.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. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Nature genetics |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
EADB |
|
dc.subject |
GR@ACE |
|
dc.subject |
DEGESCO |
|
dc.subject |
EADI |
|
dc.subject |
GERAD |
|
dc.subject |
Demgene |
|
dc.subject |
FinnGen |
|
dc.subject |
ADGC |
|
dc.subject |
CHARGE |
|
dc.subject |
Humans |
|
dc.subject |
Alzheimer Disease |
|
dc.subject |
tau Proteins |
|
dc.subject |
Genome-Wide Association Study |
|
dc.subject |
Cognitive Dysfunction |
|
dc.subject |
Alzheimer's Disease |
|
dc.subject |
Neurosciences |
|
dc.subject |
Genetics |
|
dc.subject |
Dementia |
|
dc.subject |
Aging |
|
dc.subject |
Prevention |
|
dc.subject |
Acquired Cognitive Impairment |
|
dc.subject |
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
Genetic Testing |
|
dc.subject |
Human Genome |
|
dc.subject |
Brain Disorders |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
2 Aetiology |
|
dc.subject |
Neurological |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Genetics & Heredity |
|
dc.subject |
GENOME-WIDE ASSOCIATION |
|
dc.subject |
NECROSIS-FACTOR-ALPHA |
|
dc.subject |
RISK LOCI |
|
dc.subject |
PREDICTION MODELS |
|
dc.subject |
AMYLOID-BETA |
|
dc.subject |
METAANALYSIS |
|
dc.subject |
VARIANTS |
|
dc.subject |
GENERATION |
|
dc.subject |
IMPUTATION |
|
dc.subject |
RESPONSES |
|
dc.subject |
06 Biological Sciences |
|
dc.subject |
11 Medical and Health Sciences |
|
dc.title |
New insights into the genetic etiology of Alzheimer's disease and related dementias. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41588-022-01024-z |
|
pubs.issue |
4 |
|
pubs.begin-page |
412 |
|
pubs.volume |
54 |
|
dc.date.updated |
2022-07-21T23:43:58Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
35379992 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/35379992 |
|
pubs.end-page |
436 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Research Support, U.S. Gov't, Non-P.H.S. |
|
pubs.subtype |
Journal Article |
|
pubs.subtype |
Research Support, N.I.H., Extramural |
|
pubs.elements-id |
893466 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Nursing |
|
dc.identifier.eissn |
1546-1718 |
|
dc.identifier.pii |
10.1038/s41588-022-01024-z |
|
pubs.record-created-at-source-date |
2022-07-22 |
|
pubs.online-publication-date |
2022-04 |
|