Identifying candidate genes and drug targets for Alzheimer's disease by an integrative network approach using genetic and brain region-specific proteomic data.

ABSTRACT: Genome-wide association studies (GWAS) have identified more than 75 genetic variants associated with Alzheimer's disease (ad). However, how these variants function and impact protein expression in brain regions remain elusive. Large-scale proteomic datasets of ad postmortem brain tissues have become available recently. In this study, we used these datasets to investigate brain region-specific molecular pathways underlying ad pathogenesis and explore their potential drug targets. We applied our new network-based tool, Edge-Weighted Dense Module Search of GWAS (EW_dmGWAS), to integrate ad GWAS statistics of 472 868 individuals with proteomic profiles from two brain regions from two large-scale ad cohorts [parahippocampal gyrus (PHG), sample size n = 190; dorsolateral prefrontal cortex (DLPFC

SUBMITTER: Liu A 

PROVIDER: S-EPMC9523561 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature