Exploring the Genetic Association of the ABAT Gene with Alzheimer ’s Disease

In this study, we performed an integrative study at the genetic and expression levels to investigate the potential genetic association between theABAT gene and AD. Through re-analyzing data from the currently largest meta-analysis of AD genome-wide association study (GWAS), we identified genetic variants in the 3 ’-UTR ofABAT as the top AD-associated SNPs (P <  1 × 10−4) in this gene. Functional annotation of these AD-associated SNPs indicated that these SNPs are located in the regulatory regions of transcription factors or/and microRNAs. Expression quantitative trait loci (eQTL) analysis and luciferase reporter assay showed that the AD risk alleles of these SNPs were associated with a reduced expression level ofABAT. Further analysis of mRNA expression data and single-cell transcriptome data of AD patients showed thatABAT reduction in the neuron is an early event during AD development. Overall, our results indicated thatABAT genetic variants may be associated with AD through affecting its mRNA expression. An abnormal level ofABAT will lead to a disturbance of the GABAergic signal pathway in AD brains.
Source: Molecular Neurobiology - Category: Neurology Source Type: research