A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease.

ABSTRACT: We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10(-4), P FDR = 9.34 × 1

SUBMITTER: Velez JI 

PROVIDER: S-EPMC4753688 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature