Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS meta-analysis, biological network...

Area of Science:

• Genomics and Bioinformatics
• Vascular Biology
• Non-communicable Diseases

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with high mortality.
• Understanding AAA's molecular basis is critical for developing effective screening, diagnostic, and therapeutic strategies.

Purpose of the Study:

• To identify novel genetic variants and genes associated with AAA through a meta-analysis of genome-wide association studies (GWASs).
• To explore the functional implications of these genetic findings and identify potential therapeutic targets for AAA.

Main Methods:

• Conducted a meta-analysis of GWASs to identify single nucleotide polymorphisms (SNPs) associated with AAA.
• Utilized expression quantitative trait loci (eQTL) and transcriptome-wide association study (TWAS) analyses to identify differentially expressed genes (DEGs).
• Constructed a protein-protein interaction (PPI) network, performed drug repurposing, and validated drug candidates using molecular docking.

Main Results:

• Identified 42 novel disease-associated SNPs and 52 previously unreported disease-related genes.
• Highlighted key biological pathways including lipid metabolism, tissue remodeling, and acetylcholine activation.
• Prioritized CD40 and LRP1 as key proteins, with abciximab, paclitaxel, and ivermectin suggested as potential therapeutic agents.

Conclusions:

• An integrative bioinformatics approach linking genomics, transcriptomics, network biology, and structural modeling provides valuable insights into AAA.
• Identified novel genetic associations and potential therapeutic strategies, including drug repurposing for AAA treatment.