Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms

Area of Science:

• Genetics
• Cardiovascular Disease Research
• Bioinformatics

Background:

• Abdominal aortic aneurysms (AAA) are complex, multifactorial diseases with severe outcomes.
• Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with AAA.
• The precise pathological roles of these SNPs and their interaction with risk factors remain unclear.

Purpose of the Study:

• To integrate and analyze 86 AAA-associated SNPs from GWAS and clinical data.
• To investigate the phenotypical vulnerabilities and associations of these SNPs with AAA risk factors.
• To elucidate the underlying genetic and molecular mechanisms driving AAA pathogenesis.

Main Methods:

• SNP data from GWAS and literature were compiled.
• The snpXplorer AnnotateMe tool was used for SNP annotation (position, MAF, CADD, pathogenicity, consequence, gene).
• Gene enrichment analysis (Gene Ontology, REVIGO) and network analysis (GeneMANIA in Cytoscape) were performed.

Main Results:

• Fifteen SNPs affecting 20 genes with a CADD score >10 were identified, primarily on chromosomes 3 and 9.
• The rs5516 SNP showed high frequency in AAA and was linked to proinflammatory and vascular remodeling phenotypes.
• SNP presence correlated positively with hypertension, dyslipidemia, and smoking history.

Conclusions:

• AAA-associated SNPs and their genes regulate lipid metabolism, extracellular matrix organization, smooth muscle cell proliferation, and oxidative stress.
• Genetic abnormalities contribute to AAA traits by influencing these biological pathways.
• This study provides a library of inborn SNPs and associated genes, revealing pathological signaling relevant to AAA development.