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

Neurobiology of Aging
Elise CuyversBELNEU Consortium and of the EU EOD Consortium

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 th...Continue Reading

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Citations

Feb 3, 2016·Translational Psychiatry·M J KeoghP F Chinnery
Sep 29, 2015·Human Mutation·Rita CacaceUNKNOWN Belgium Neurology (BELNEU) Consortium and the European Early-Onset Dementia (EU EOD) Consortium
Oct 25, 2016·Neurobiology of Aging·Qiang GangUNKNOWN Muscle Study Group and The International IBM Genetics Consortium
Jun 3, 2020·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Ellen GelpiGabor G Kovacs
Feb 20, 2018·The Journal of Clinical Investigation·YouJin LeeBjarne Udd
Sep 27, 2020·Calcified Tissue International·Judit DonáthGyula Poór
Sep 18, 2020·International Journal of Molecular Sciences·Sharmeelavathi KrishnanPrashant Bharadwaj
Aug 24, 2020·Redox Biology·Nachiyappan VenkatachalamStanislav Engel
May 23, 2020·Neurobiology of Disease·Rita GuerreiroJose Bras

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