BACKGROUND & AIMS: Cardiometabolic traits are complex interrelated traits that result from a combination of genetic and lifestyle factors. This study aimed to assess the interaction between genetic variants and dietary macronutrient intake on cardiometabolic traits [body mass index, waist circumference, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triacylglycerol, systolic blood pressure, diastolic blood pressure, fasting serum glucose, fasting serum insulin, and glycated haemoglobin]. METHODS: This cross-sectional study consisted of 468 urban young adults aged 20 ± 1 years, and it was conducted as part of the Study of Obesity, Nutrition, Genes and Social factors (SONGS) project, a sub-study of the Young Lives study. Thirty-nine single nucleotide polymorphisms (SNPs) known to be associated with cardiometabolic traits at a genome-wide significance level (P <
5 × 10 RESULTS: There were no significant associations between the GRS and any of the cardiometabolic traits. However, a significant interaction was observed between the GRS and carbohydrate intake on HDL-C concentration (P CONCLUSIONS: Our results suggest that young adults who consume a higher carbohydrate diet and have a higher GRS have a lower HDL-C concentration, which in turn is linked to cardiovascular diseases, and indicate that personalised nutrition strategies targeting a reduction in carbohydrate intake might be beneficial for these individuals.