Interactions Between Genetic Risk and Macronutrient Intake on Obesity-Related Traits in Sri Lankan Adults

Background/Objectives: In Sri Lanka, where obesity is increasingly prevalent, evidence on gene–diet interactions involving macronutrient intake and composition remains limited. We therefore examined these interactions on obesity-related traits. Methods: This cross-sectional analysis included 398 adults (mean age, 42.5 ± 8.3 years; 60.8% men). Anthropometric measurements defined increased body mass index (BMI) and waist circumference (WC). Dietary macronutrient intake was assessed with a validated tool, and carbohydrate/fat intake patterns were determined based on study population-specific macronutrient cutoffs and interpreted as relative dietary patterns rather than clinically defined diets. A genetic risk score (GRS) was constructed using three single-nucleotide polymorphisms (FTO rs8050136, rs1588413, and TCF7L2 rs7903146). Associations and interaction effects were examined after adjustment for relevant confounders. Results: The GRS was positively associated with increased WC (p = 0.032). Carbohydrate/fat intake pattern was associated with increased BMI (p = 0.044) and WC (p = 0.021), with lower odds in the high-carbohydrate/low-fat and other combination patterns than in the low-carbohydrate/high-fat reference group. Significant GRS–carbohydrate interactions were observed for increased BMI (pinteraction = 0.008) and WC (pinteraction = 0.033), with higher odds among high-GRS individuals in the low-carbohydrate group. A GRS–fat interaction was also observed for increased BMI (pinteraction = 0.03), with significantly higher odds among high-GRS individuals in the high-fat group. Within the low-carbohydrate/high-fat pattern, high-GRS individuals had higher odds of increased BMI (OR= 3.1, p = 0.014). Conclusions: Dietary carbohydrate and fat intakes may influence the association between genetic susceptibility and obesity in Sri Lankan adults, particularly under a relatively low-carbohydrate/high-fat pattern.