Differential burden of rare protein truncating variants in Alzheimer's disease patients compared to centenarians.

ABSTRACT: We compared coding region variants of 53 cognitively healthy centenarians and 45 patients with Alzheimer's disease (AD), all of Ashkenazi Jewish (AJ) ancestry. Despite the small sample size, the known AD risk variant APOE4 reached genome-wide significance, indicating the advantage of utilizing 'super-controls'. We restricted our subsequent analysis to rare variants observed at most once in the 1000 Genomes database and having a minor allele frequency below 2% in our AJ sample. We compared the burden of predicted protein altering variants between cases and controls as normalized by the level of rare synonymous variants. We observed an increased burden among AD subjects for predicted loss-of-function (LoFs) variants defined as stop-gain, frame shift, initiation codon (INIT) and splice site m

SUBMITTER: Freudenberg-Hua Y 

PROVIDER: S-EPMC5181592 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature