Genetic insights into coronary heart disease: A multi-omics approach

Abstract

Aim: Coronary heart disease (CHD) is a leading cause of mortality worldwide, with a complex interplay of genetic and environmental factors influencing its development. Genome-wide association studies (GWAS) have identified multiple genetic loci associated with CHD, providing crucial insights into its pathophysiology. However, the full spectrum of genetic contributors and their biological mechanisms remains to be elucidated. Methodology: This study integrates GWAS data with various ontology analyses to identify key genetic determinants of CHD. Variants associated with CHD were retrieved from public datasets and analysed using bioinformatics tools to explore their biological significance. Pathway enrichment, protein-protein interaction (PPI) networks, and clustering algorithms delineated functional relationships among candidate genes. Additionally, microRNA (miRNA) interactions were assessed to understand post-transcriptional regulatory mechanisms. Results: These findings revealed novel insights into CHD genetics, confirming known loci such as 9p21.3 (CDKN2B-AS1), COL4A2 and PHACTR1, while uncovering their broader functional roles in vascular remodelling, inflammation, and lipid metabolism. Enrichment and miRNA analyses highlighted new regulatory layers involving TGF-beta and AGE-RAGE pathways, and miRNAs like hsa-miR-147b and hsa-miR-4790-5p, suggesting previously unrecognized mechanisms in CHD pathogenesis. Interpretation: This study contributes to understanding CHD genetics by integrating multi-omic data to highlight relevant genetic factors and associated biological pathways. Key words: Coronary heart disease, Functional enrichment analysis, Genome-wide association studies, Genetic risk factors, Precision medicine