From Food Choice to Nutrigenomic Response: Integrating Nutrigenetics and Nutrigenomics Toward Precision Nutrition

Nutrigenetics and nutrigenomics represent complementary dimensions of the complex relationship between diet and the human genome and provide a conceptual basis for precision nutrition. Nutrigenetics investigates how interindividual genetic variability influences food perception, dietary behavior, nutrient metabolism, and biological responses, whereas nutrigenomics explores how nutrients and bioactive food components modulate gene expression, signaling pathways, and epigenetic mechanisms. Importantly, these processes are interconnected: genetic variation may influence dietary exposure itself through effects on sensory perception, food preferences, appetite, and eating behavior, while additional genetic differences can modify nutrient absorption, metabolism, bioavailability, and downstream molecular responses. This review integrates these interactions within a diet–genome–phenotype framework, incorporating nutrient-responsive molecular pathways, epigenetic regulation, and the gut microbiota as additional determinants of interindividual variability. Overweight and obesity are examined as a paradigmatic application of this framework, illustrating how genetic determinants of dietary exposure and metabolic response may jointly contribute to susceptibility and heterogeneous responses to nutritional interventions. We further propose a research-oriented Weighted Evidence Score (WES) for the evidence-based prioritization of candidate genetic variants, integrating seven domains of functional evidence, phenotypic evidence, independent replication, genotype–diet interactions, nutritional intervention evidence, incremental predictive value, and population validity. In a pilot application to twelve illustrative variants or haplotypes, eight were classified as Tier 2 and four as Tier 3, with none meeting the requirements for Tier 1. Rather than representing an immediately actionable clinical test, such a research-oriented panel is intended as a dynamic hypothesis-generating and validation tool integrating genotype with dietary exposure, metabolic and molecular biomarkers, lifestyle factors, and phenotypic outcomes. Particular emphasis is placed on distinguishing evidence-based research prioritization from the additional validation required for clinical actionability. Finally, ethical, professional, and social challenges related to genomic information, including informed consent, privacy, communication, population diversity, and equitable implementation, are considered. Precision nutrition should ultimately be defined not by the amount of molecular information collected, but by its demonstrated ability to provide incremental predictive value and improve nutritional interventions beyond what can be achieved using established clinical, dietary, and population-based approaches.