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 journalArticle

12 Citations (Scopus)

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 p.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
Volume36
Issue number5
DOIs
Publication statusPublished - 2015

Fingerprint

Dementia
Alzheimer Disease
Meta-Analysis
Genome-Wide Association Study
Gene Frequency
Confidence Intervals
Genes

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Cuyvers, E., van der Zee, J., Bettens, K., Engelborghs, S., Vandenbulcke, M., Robberecht, C., ... Sleegers, K. (2015). Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: A European early-onset dementia consortium study. Neurobiology of Aging, 36(5), 2005.e15-2005.e22. https://doi.org/10.1016/j.neurobiolaging.2015.02.014

Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia : A European early-onset dementia consortium study. / Cuyvers, Elise; van der Zee, Julie; Bettens, Karolien; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Robberecht, Caroline; Dillen, Lubina; Merlin, Céline; Geerts, Nathalie; Graff, Caroline; Thonberg, Håkan; Chiang, Huei Hsin; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A.; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Nacmias, Benedetta; Sorbi, Sandro; Sanchez-Valle, Raquel; Lladó, Albert; Gelpi, Ellen; Almeida, Maria Rosário; Santana, Isabel; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matěj, Radoslav; Rohan, Zdenek; Ruiz, Agustín; Frisoni, Giovanni B.; Fabrizi, Gian Maria; Vandenberghe, Rik; De Deyn, Peter P.; Van Broeckhoven, Christine; Sleegers, Kristel.

In: Neurobiology of Aging, Vol. 36, No. 5, 2015, p. 2005.e15-2005.e22.

Research output: Contribution to journalArticle

Cuyvers, E, van der Zee, J, Bettens, K, Engelborghs, S, Vandenbulcke, M, Robberecht, C, Dillen, L, Merlin, C, Geerts, N, Graff, C, Thonberg, H, Chiang, HH, Pastor, P, Ortega-Cubero, S, Pastor, MA, Diehl-Schmid, J, Alexopoulos, P, Benussi, L, Ghidoni, R, Binetti, G, Nacmias, B, Sorbi, S, Sanchez-Valle, R, Lladó, A, Gelpi, E, Almeida, MR, Santana, I, Clarimon, J, Lleó, A, Fortea, J, de Mendonça, A, Martins, M, Borroni, B, Padovani, A, Matěj, R, Rohan, Z, Ruiz, A, Frisoni, GB, Fabrizi, GM, Vandenberghe, R, De Deyn, PP, Van Broeckhoven, C & Sleegers, K 2015, 'Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: A European early-onset dementia consortium study', Neurobiology of Aging, vol. 36, no. 5, pp. 2005.e15-2005.e22. https://doi.org/10.1016/j.neurobiolaging.2015.02.014
Cuyvers, Elise ; van der Zee, Julie ; Bettens, Karolien ; Engelborghs, Sebastiaan ; Vandenbulcke, Mathieu ; Robberecht, Caroline ; Dillen, Lubina ; Merlin, Céline ; Geerts, Nathalie ; Graff, Caroline ; Thonberg, Håkan ; Chiang, Huei Hsin ; Pastor, Pau ; Ortega-Cubero, Sara ; Pastor, Maria A. ; Diehl-Schmid, Janine ; Alexopoulos, Panagiotis ; Benussi, Luisa ; Ghidoni, Roberta ; Binetti, Giuliano ; Nacmias, Benedetta ; Sorbi, Sandro ; Sanchez-Valle, Raquel ; Lladó, Albert ; Gelpi, Ellen ; Almeida, Maria Rosário ; Santana, Isabel ; Clarimon, Jordi ; Lleó, Alberto ; Fortea, Juan ; de Mendonça, Alexandre ; Martins, Madalena ; Borroni, Barbara ; Padovani, Alessandro ; Matěj, Radoslav ; Rohan, Zdenek ; Ruiz, Agustín ; Frisoni, Giovanni B. ; Fabrizi, Gian Maria ; Vandenberghe, Rik ; De Deyn, Peter P. ; Van Broeckhoven, Christine ; Sleegers, Kristel. / 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, No. 5. pp. 2005.e15-2005.e22.
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AU - Engelborghs, Sebastiaan

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AU - Robberecht, Caroline

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AU - Merlin, Céline

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AU - Thonberg, Håkan

AU - Chiang, Huei Hsin

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AU - Alexopoulos, Panagiotis

AU - Benussi, Luisa

AU - Ghidoni, Roberta

AU - Binetti, Giuliano

AU - Nacmias, Benedetta

AU - Sorbi, Sandro

AU - Sanchez-Valle, Raquel

AU - Lladó, Albert

AU - Gelpi, Ellen

AU - Almeida, Maria Rosário

AU - Santana, Isabel

AU - Clarimon, Jordi

AU - Lleó, Alberto

AU - Fortea, Juan

AU - de Mendonça, Alexandre

AU - Martins, Madalena

AU - Borroni, Barbara

AU - Padovani, Alessandro

AU - Matěj, Radoslav

AU - Rohan, Zdenek

AU - Ruiz, Agustín

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