Abstract/Summary

Background: Metabolic diseases, like type 2 diabetes mellitus and obesity, show a growing public health concern in Sri Lanka. Genetic predisposition and diet contribute to metabolic disease risk, but there are limited investigations into the impact of gene–diet interactions on metabolic disease risk in the Sri Lankan population. In this study, we examined whether a metabolic genetic risk score (GRS), constructed from 10 single nucleotide polymorphisms (SNPs), interacts with dietary factors to influence metabolic health indicators in Sri Lankan adults. Methods: This cross-sectional study included 105 generally healthy adults aged 25–50 years from the GOOD (Genetics of Obesity and Diabetes) study. Anthropometric, biochemical, and dietary data using food frequency questionnaires were collected using validated methods. Genotyping was performed using the KASP® assay. The unweighted GRS was calculated by summing risk alleles across 10 SNPs in the TCF7L2, CAPN10, FTO KCNJ11, and MC4R genes. Gene–diet interaction analysis was conducted using regression models adjusted for confounders. Results: A statistically significant interaction was identified between the 10-SNP metabolic GRS and polyunsaturated fatty acid (PUFA) intake on waist circumference (P(interaction) = 0.00009). Participants with a high GRS (≥6 risk alleles) and higher PUFA intake (≥3.1 g/day) exhibited significantly lower waist circumference (p = 0.047). Conclusions: This study provides novel insights to understand gene–diet interactions affecting metabolic traits in Sri Lankans. The findings suggest that higher PUFA intake may mitigate genetic susceptibility to central obesity, highlighting the importance of personalized dietary recommendations for metabolic disease prevention. Further studies in larger cohorts are warranted to confirm this finding.