Genetic Variants in Metabolic Pathways and Their Role in Cardiometabolic Risk: An Observational Study of >4000 Individuals.

Obesity, a major risk factor for cardiometabolic traits, is influenced by both genetic and environmental factors. Genetic studies have identified multiple single-nucleotide polymorphisms (SNPs) associated with obesity and related traits. This study aimed to examine the association between genetic risk score (GRS) and obesity-associated traits, while incorporating SNPs with established gene-diet interactions to explore their potential role in precision nutrition (PN) strategies. : A total of 4279 participants were stratified into low- and intermediate-/high-GRS groups based on 18 SNPs linked to obesity and cardiometabolic traits. This study followed a case-control design, where cases included individuals with overweight/obesity, T2DM-positive (+), or CVD-positive (+) individuals and controls, which comprised individuals free of these traits. Logistic regression area under the curve (AUC) models were used to assess the predictive power of the GRS and traditional risk factors on BMI, T2DM and CVD. : Individuals in the intermediate-/high-GRS group had higher odds of being overweight or obese (OR = 1.23, CI: 1.03-1.48, = 0.02), presenting as T2DM+ (OR = 1.56, CI: 1.03-2.49, = 0.03) and exhibiting CVD-related traits (OR = 1.56, CI: 1.25-1.95, < 0.0001), compared to the low-GRS group. The GRS was the second most predictive factor after age for BMI (AUC = 0.515; 95% CI: 0.462-0.538). The GRS also demonstrated a predictive power of 0.528 (95% CI: 0.508-0.564) for CVD and 0.548 (95% CI: 0.440-0.605) for T2DM. : This study supports the potential utility of the GRS in assessing obesity and cardiometabolic risk, while emphasizing the potential of PN approaches in modulating genetic susceptibility. Incorporating gene-diet interactions provides actionable insights for personalized dietary strategies. Future research should integrate multiple gene-diet and gene-gene interactions to enhance risk prediction and targeted interventions.