Obesity genes: implication in childhood obesity

Overweight and obesity prevalence has dramatically increased during the last decade and reached epidemic dimensions. By 2030 it is expected that there will be 2.16 billion overweight individuals with 1.12 billion adults predicted to be clinically obese. Obesity is caused by both genetic and non-genetic factors. BMI as a common measure of obesity is a highly heritable trait with heritability estimates of ∼0.7 for both adults and children. Mutations in a few genes such as LEPR and MC4R identified by molecular genetic analysis in children are known to be involved in rare monogenic severe obesity. Their identification opened important insights in fundamental pathways, in particular the leptin-melanocortin pathway, involved in control of appetite and energy metabolism. However, the polygenic basis of common obesity with many common variants conferring each modest risk to the phenotype is still one of the major challenges in genetics of obesity. Driven by the availability of genome wide association (GWAS) technology enabling analysis of millions of markers in thousands of individuals, multiple polymorphisms/genes have been identified in the last 5 years. With common genetic variants in genes such as FTO (fat mass and obesity-associated gene) a great number of additional susceptibility variants have been identified altogether still accounting for a small percentage of the overall risk for obesity. This review outlines the progress of research in genetics of obesity during recent years in adults and children.