Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia : A European early-onset dementia consortium study
Cuyvers, Elise (University of Antwerp (Bèlgica))
Van der Zee, Julie (University of Antwerp (Bèlgica))
Bettens, Karolien (University of Antwerp (Bèlgica))
Engelborghs, Sebastiaan (University of Antwerp (Bèlgica))
Vandenbulcke, Mathieu (University Hospitals Leuven Gasthuisberg (Bèlgica))
Robberecht, Caroline (University of Antwerp (Bèlgica))
Dillen, Lubina (University of Antwerp (Bèlgica))
Merlin, Céline (University of Antwerp (Bèlgica))
Geerts, Nathalie (University of Antwerp (Bèlgica))
Graff, Caroline (Karolinska University Hospital and Karolinska Institutet (Suècia))
Thonberg, Håkan (Karolinska University Hospital and Karolinska Institutet (Suècia))
Chiang, Huei-Hsin (Karolinska Institutet (Estocolm, Suècia))
Pastor, Pau (Instituto de Salud Carlos III)
Ortega-Cubero, Sara (Instituto de Salud Carlos III)
Pastor, Maria A. (Instituto de Salud Carlos III)
Diehl-Schmid, Janine (Technische Universität München)
Alexopoulos, Panagiotis (Technische Universität München)
Benussi, Luisa (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Ghidoni, Roberta (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Binetti, Giuliano (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Nacmias, Benedetta (Università degli Studi di Firenze)
Sorbi, Sandro (Università degli Studi di Firenze)
Sanchez-Valle, Raquel (Hospital Clínic i Provincial de Barcelona)
Llado Plarrumani, Albert (Hospital Clínic i Provincial de Barcelona)
Gelpi, Ellen (Hospital Clínic i Provincial de Barcelona)
Almeida, Maria Rosário (University of Coimbra (Portugal))
Santana, Isabel (University of Coimbra (Portugal))
Clarimón, Jordi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
de Mendonça, Alexandre (University of Lisbon)
Martins, Madalena (University of Lisbon)
Borroni, Barbara (University of Brescia (Itàlia))
Padovani, Alessandro (University of Brescia (Itàlia))
Matej, Radoslav (Charles University in Prague)
Rohan, Zdenek (Charles University in Prague)
Ruiz Laza, Agustín (Institut Català de Neurociències Aplicades)
Frisoni, Giovanni B. (Université de Genève)
Fabrizi, Gian Maria (University of Verona)
Vandenberghe, Rik (University of Leuven (Bèlgica))
De Deyn, Peter Paul (University of Groningen (Països Baixos))
Van Broeckhoven, Christine (University of Antwerp (Bèlgica))
Sleegers, Kristel (University of Antwerp (Bèlgica))
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2015
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 ratio= 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.
Grants:	Ministerio de Ciencia e Innovación PI11/00234 Ministerio de Economía y Competitividad PI12/01311 Ministerio de Economía y Competitividad PI13/02434
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; European early-onset dementia consortium ; Meta-analysis ; Rare variants ; SQSTM1/p62
Published in:	Neurobiology of Aging, Vol. 36 Núm. 5 (2015) , p. 2005.e15-2005.e22, ISSN 1558-1497

DOI: 10.1016/j.neurobiolaging.2015.02.014
PMID: 25796131

8 p, 511.1 KB

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Articles > Research articles
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