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

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