An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer's disease.

ABSTRACT: Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). We observed strong association between VNTR length and a genome-wide associated signal for AD in the ABCA7 locus. Expanded VNTR alleles were highly enriched in AD patients [odds ratio = 4.5 (1.3-24.2)], and VNTR length inversely correlated with amyloid β_1-42 in cerebrospinal fluid and ABCA7 expr

SUBMITTER: De Roeck A 

PROVIDER: S-EPMC5954066 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature