Identification of Disease-Related Genes That Are Common between Alzheimer’s and Cardiovascular Disease Using Blood Genome-Wide Transcriptome Analysis

Abstract

Accumulating evidence has suggested a shared pathophysiology between Alzheimer’s disease (AD) and cardiovascular disease (CVD). Based on genome-wide transcriptomes, specifically those of blood samples, we identify the shared disease-related signatures between AD and CVD. In addition to gene expressions in blood, the following prior knowledge were utilized to identify several candidate disease-related gene (DRG) sets: protein–protein interactions, transcription factors, disease–gene relationship databases, and single nucleotide polymorphisms. We selected the respective DRG sets for AD and CVD that show a high accuracy for disease prediction in bulk and single-cell gene expression datasets. Then, gene regulatory networks (GRNs) were constructed from each of the AD and CVD DRG sets to identify the upstream regulating genes. Using the GRNs, we identified two common upstream genes (GPBP1 and SETDB2) between the AD and CVD GRNs. In summary, this study has identified the potential AD- and CVD-related genes and common hub genes between these sets, which may help to elucidate the shared mechanisms between these two diseases.

Keywords

• Alzheimer’s disease
• cardiovascular disease
• blood gene expression
• disease-related molecular signatures
• differential expression analysis
• gene regulatory network