en
Scientific article
English

Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study

ContributorsFrisoni, Giovanni
Published inNeurobiology of aging, vol. 36, no. 5, p. 2005.e15-e22
Publication date2015
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 Alzheimer's 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 = 1-1.22], 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.

Citation (ISO format)
FRISONI, Giovanni. Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study. In: Neurobiology of aging, 2015, vol. 36, n° 5, p. 2005.e15–e22. doi: 10.1016/j.neurobiolaging.2015.02.014
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0197-4580
455views
2downloads

Technical informations

Creation08/20/2015 11:20:00 AM
First validation08/20/2015 11:20:00 AM
Update time03/14/2023 11:40:59 PM
Status update03/14/2023 11:40:58 PM
Last indexation01/16/2024 7:07:12 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack