Title
Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia : a European early-onset dementia consortium studyGenetic variability in SQSTM1 and risk of early-onset Alzheimer dementia : a European early-onset dementia consortium study
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
VIB DMG - Neurodegenerative Brain Diseases Group
Neurochemistry and behaviour
VIB DMG - Applied Molecular Genomics
VIB DMG - Molecular Neurogenomics
Publication type
article
Publication
Fayetteville, N.Y.,
Subject
Biology
Human medicine
Source (journal)
Neurobiology of aging. - Fayetteville, N.Y.
Volume/pages
36(2015):5, 8 p.
ISSN
0197-4580
ISI
000355100900025
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European early-onset dementia cohorts (926 early-onset Alzheimers disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292= and p.R312= showed nominal association with AD (odds ratiop.D292= = 1.11 [95% confidence interval = 11.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/2bb004/01204b7d.pdf
E-info
https://repository.uantwerpen.be/docman/iruaauth/2ba951/93f9745.pdf
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