Nutrigenomics and Personalized Nutrition: Molecular Insights Into Metabolic Health and Disease Prevention

Complex interactions between genetic variation, nutrition, lipid metabolism and environmental exposures play a role in metabolic diseases. While nutrigenomics is growing in significance for precision nutrition studies, systems level (whole organism) characterization of metabolic nutrigenomic interactions is underdeveloped. This study investigated nutrigenomic associations linked to metabolic health and disease prevention using statistical, network-based, and functional enrichment approaches. A curated dataset containing experimentally validated gene–trait associations was analyzed using computational workflows, including disease categorization, descriptive statistical analysis, hub-gene prioritization, gene–trait interaction network construction, and pathway enrichment analysis. The dataset comprised 144,377 metabolic nutrigenomic records involving 194 genes, 541 SNPs, 392 disease traits, and 3,535 PubMed references. Cardiovascular lipid disorders represented the dominant disease category, followed by liver NAFLD and obesity. Network-centrality analysis identified ZPR1, GCKR, APOE, and PCSK9 as the most interconnected hub genes across metabolic phenotypes. Additional genes, including LPL, APOB, ANGPTL4, TM6SF2, LPA, and LIPG, formed interconnected metabolic modules associated with lipid transport, triglyceride regulation, and hepatic fat metabolism. Functional enrichment analysis demonstrated significant overrepresentation of pathways related to cholesterol homeostasis, triglyceride metabolism, cholesterol metabolism, PPAR signaling, plasma lipoprotein remodeling, chylomicron clearance, and HDL remodeling. These findings indicate that metabolic nutrigenomic associations are predominantly organized around lipid-regulatory biology and lipoprotein dynamics. The results support a systems-level framework for personalized nutrition in which interconnected metabolic pathways and gene networks may contribute to targeted strategies for metabolic disease prevention and nutritional intervention.