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

Elise Cuyvers, Julie van der Zee, Karolien Bettens, Sebastiaan Engelborghs, Mathieu Vandenbulcke, Caroline Robberecht, Lubina Dillen, Céline Merlin, Nathalie Geerts, Caroline Graff, Håkan Thonberg, Huei Hsin Chiang, Pau Pastor, Sara Ortega-Cubero, Maria A. Pastor, Janine Diehl-Schmid, Panagiotis Alexopoulos, Luisa Benussi, Roberta Ghidoni, Giuliano BinettiBenedetta Nacmias, Sandro Sorbi, Raquel Sanchez-Valle, Albert Lladó, Ellen Gelpi, Maria Rosário Almeida, Isabel Santana, Jordi Clarimon, Alberto Lleó, Juan Fortea, Alexandre de Mendonça, Madalena Martins, Barbara Borroni, Alessandro Padovani, Radoslav Matěj, Zdenek Rohan, Agustín Ruiz, Giovanni B. Frisoni, Gian Maria Fabrizi, Rik Vandenberghe, Peter P. De Deyn, Christine Van Broeckhoven, Kristel Sleegers

    Research output: Contribution to journalArticleResearchpeer-review

    24 Citations (Scopus)


    © 2015 The Authors. 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.
    Original languageEnglish
    Pages (from-to)2005.e15-2005.e22
    JournalNeurobiology of Aging
    Issue number5
    Publication statusPublished - 1 Jan 2015


    • Alzheimer's disease
    • European early-onset dementia consortium
    • Meta-analysis
    • Rare variants
    • SQSTM1/p62


    Dive into the research topics of 'Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: A European early-onset dementia consortium study'. Together they form a unique fingerprint.

    Cite this