Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis.
APOE
Alzheimer's
Epistasis
GWAS
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
03
05
2022
revised:
04
07
2022
accepted:
23
07
2022
pubmed:
18
8
2022
medline:
20
9
2022
entrez:
17
8
2022
Statut:
ppublish
Résumé
The APOE-ε4 allele is known to predispose to amyloid deposition and consequently is strongly associated with Alzheimer's disease (AD) risk. There is debate as to whether the APOE gene accounts for all genetic variation of the APOE locus. Another question which remains is whether APOE-ε4 carriers have other genetic factors influencing the progression of amyloid positive individuals to AD. We conducted a genome-wide association study in a sample of 5,390 APOE-ε4 homozygous (ε4ε4) individuals (288 cases and 5102 controls) aged 65 or over in the UK Biobank. We found no significant associations of SNPs in the APOE locus with AD in the sample of ε4ε4 individuals. However, we identified a novel genome-wide significant locus associated to AD, mapping to DAB1 (rs112437613, OR = 2.28, CI = 1.73-3.01, p = 5.4 × 10
Identifiants
pubmed: 35977442
pii: S0197-4580(22)00163-4
doi: 10.1016/j.neurobiolaging.2022.07.009
pmc: PMC9548409
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Apolipoprotein E4
0
DAB1 protein, human
0
Nerve Tissue Proteins
0
Reelin Protein
0
RELN protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-76Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T033371/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure statement The authors report no competing interests.
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