Genetic Influences on Macronutrient Preferences and Their Impact on Childhood Food Intake and Metabolic Health

Highlight

This longitudinal study demonstrates that genetic predisposition to higher carbohydrate intake influences youth consumption of sugar-sweetened beverages and fast food. In contrast, a higher genetic propensity for protein intake correlates with reduced consumption of sugary drinks. No consistent associations between these genetic scores and cardiometabolic health markers were found at age 18. Gene enrichment analysis links these intake behaviors to specific hypothalamic cell types implicated in nutrient-specific appetite regulation.

Study Background

Understanding the determinants of dietary intake in childhood and adolescence is critical for addressing the rising burden of obesity and cardiometabolic diseases. While environmental and social factors partly shape food preferences, genetic influences on macronutrient intake may importantly contribute to individual differences in diet quality. However, the extent to which genetic predispositions for carbohydrate, fat, and protein consumption manifest in specific food choices and impact metabolic health during development remains incompletely understood. This study aims to elucidate these relationships using polygenic scores derived from adult genome-wide association studies (GWAS) to explore associations with dietary patterns and cardiometabolic outcomes in youth.

Study Design

The study leveraged genetic and phenotypic data from 516 non-Hispanic White children enrolled in the prospective Project Viva cohort. Polygenic scores (PS) for carbohydrate, fat, and protein intake were constructed based on large adult GWAS datasets. Dietary intake was assessed longitudinally at approximately ages 3, 8, 13, and 18 years, including consumption frequency of sugar-sweetened beverages (SSB) and fast food. Anthropometric measures including BMI z scores and waist circumference were recorded, alongside cardiometabolic biomarkers—fasting glucose, insulin, glycated hemoglobin, and blood lipids—collected at 18 years. Statistical associations were evaluated with generalized estimating equations for repeated measures and regression models for cross-sectional outcomes. Additionally, gene set enrichment analyses were performed using the Human HYPOMAP dataset to identify hypothalamic cell types linked to macronutrient intake-associated genetic variants.

Key Findings

The analyses revealed that higher carbohydrate PS was significantly associated with increased odds of consuming two or more servings per week of SSB (OR 1.20; 95% CI 1.07–1.33) and at least weekly fast-food intake (OR 1.11; 95% CI 1.004–1.23) across childhood and adolescence. Conversely, elevated protein PS correlated with lower odds of SSB consumption (OR 0.84; 95% CI 0.75–0.93). Associations for fat intake PS were not highlighted as significant. Importantly, these macronutrient intake genetic scores did not show consistent relationships with BMI z scores or other cardiometabolic outcomes at age 18, including fasting glucose, insulin, HbA1c, lipids, or measures of adiposity such as waist circumference and truncal fat.

Gene enrichment investigation demonstrated that macronutrient intake-related genetic signals were localized to specific hypothalamic subregions and neurotransmitter-defined cell clusters, suggesting that genetic regulation of appetite and nutrient-specific signaling in the hypothalamus underpins individual variability in dietary preferences from supported childhood through late adolescence.

Expert Commentary

This study offers valuable insights into the biologic drivers of food choice among youth, providing genetic evidence supporting the role of carbohydrate preference in promoting consumption of energy-dense, nutrient-poor foods like sugary beverages and fast food. The lack of consistent associations with metabolic health markers at 18 years may reflect the complex multifactorial etiology of cardiometabolic risk, the relatively young age of participants, or limited power. The hypothalamic gene enrichment findings align with known neurobiological pathways controlling appetite and macronutrient-specific feeding behaviors, underscoring the plausibility of these genetic effects.

Limitations include restriction to a homogenous racial/ethnic group, which may limit generalizability, and reliance on self- or parent-reported dietary frequency, which may introduce measurement bias. Future research should extend to diverse populations, examine longer-term metabolic outcomes, and integrate environmental exposures to fully characterize gene-environment interplay in diet and disease risk.

Conclusion

Genetic predisposition to carbohydrate intake influences children’s and adolescents’ consumption of sugar-sweetened beverages and fast food, potentially mediated by hypothalamic nutrient-specific appetite pathways. Despite these dietary associations, macronutrient intake-specific polygenic scores were not consistently predictive of cardiometabolic risk by late adolescence. These findings highlight the importance of considering genetic influences on eating behaviors in nutritional interventions and public health strategies aimed at improving youth diet quality and preventing metabolic disease.

Funding and ClinicalTrials.gov

The Project Viva cohort and genetic analysis were supported by [specific funding information to be provided as per original study details]. There is no mention of clinical trial registration associated with this observational research.

References

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