The Genetic Basis of Childhood Obesity: A Systematic Review

Overweight and obesity in childhood and adolescence represents one of the most challenging public health problems of our century owing to its epidemic proportions and the associated significant morbidity, mortality, and increase in public health costs. The pathogenesis of polygenic obesity is multifactorial and is due to the interaction among genetic, epigenetic, and environmental factors. More than 1100 independent genetic loci associated with obesity traits have been currently identified, and there is great interest in the decoding of their biological functions and the gene-environment interaction. The present study aimed to systematically review the scientific evidence and to explore the relation of single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with changes in body mass index (BMI) and other measures of body composition in children and adolescents with obesity, as well as their response to lifestyle interventions. Twenty-seven studies were included in the qualitative synthesis, which consisted of 7928 overweight/obese children and adolescents at different stages of pubertal development who underwent multidisciplinary management. The effect of polymorphisms in 92 different genes was assessed and revealed SNPs in 24 genetic loci significantly associated with BMI and/or body composition change, which contribute to the complex metabolic imbalance of obesity, including the regulation of appetite and energy balance, the homeostasis of glucose, lipid, and adipose tissue, as well as their interactions. The decoding of the genetic and molecular/cellular pathophysiology of obesity and the gene-environment interactions, alongside with the individual genotype, will enable us to design targeted and personalized preventive and management interventions for obesity early in life.