Genetic Determinants of Macronutrient Intake Are Associated With Specific Food Intake in Youth: A Cohort Study Across...

We examined associations of polygenic scores (PS) for macronutrient intake with food intake and cardiometabolic outcomes during childhood and adolescence and evaluated gene enrichment in hypothalamic cell types.

We derived carbohydrate, fat, and protein intake PS from an adult genome-wide association study among 516 non-Hispanic White children from the Project Viva cohort. We estimated dietary intake and calculated BMI z scores from measured height and weight at ages ∼3, 8, 13, and 18 years. Waist circumference, truncal fat, fasting glucose, insulin, glycated hemoglobin, and blood lipids were measured at 18 years. We estimated associations of PS with sugar-sweetened beverages (SSB), fast food, and BMI z score using generalized estimating equations (longitudinal) and using regression models for cardiometabolic and secondary dietary outcomes (cross-sectional). We evaluated enrichment of macronutrient intake genetic signals in hypothalamic cell types in the Human HYPOMAP data set.

A 1-SD increase in carbohydrate PS was associated with higher odds of consuming two or more servings per week of SSB (odds ratio [OR] 1.20; 95% CI 1.07, 1.33) and one or more times per week of fast food (OR 1.11; 95% CI 1.004, 1.23) from ages 3 to 18 years. Higher-protein PS was associated with lower odds of consuming SSB (OR 0.84; 95% CI 0.75, 0.93). We did not observe consistent associations between macronutrient intake PS and cardiometabolic outcomes. We observed hypothalamic regional and neurotransmitter-specific patterns of gene enrichment for carbohydrate or protein intake.

Genetic susceptibility for carbohydrate intake is associated with SSB and fast-food consumption in youth. Underlying pathways relating to hypothalamic nutrient-specific appetite signaling may be involved.