Polygenic Childhood Obesity: Integrating Genetics and Environment for Early Intervention

Abstract – Background: Childhood obesity is a global health challenge driven by a complex interplay of genetic predispositions and environmental exposures. Genome-wide association studies have identified many obesity-associated loci, and polygenic risk scores (PRS) enable quantification of genetic susceptibility. Concurrently, lifestyle factors – including diet, physical activity, sleep, stress, and socioeconomic status – modify these genetic risks. Summary: Healthy lifestyle practices can mitigate genetic risk, while unhealthy diets and sedentary habits amplify it. The review details how PRS, by capturing the cumulative effect of numerous small-effect variants, facilitate risk stratification in children. Furthermore, gene-environment interactions – from diet and exercise to sleep, stress, and socioeconomic conditions – might inform personalized intervention strategies, including tailored nutritional guidance, behavior modification, and targeted physical activity interventions initiated early. Key Message: Understanding gene-environment interactions is essential for refining risk assessments and developing personalized, equitable public health strategies. Future research should focus on enhancing multi-ancestry PRS accuracy, elucidating underlying biological pathways, and translating genetic insights into actionable, context-specific interventions to combat childhood obesity.