<h4>Objective</h4>This study aimed to investigate the associations between functional genetic variants in leptin-melanocortin pathway and risk of childhood obesity, as well as exploring gene-lifestyle interactions on obesity risk.<h4>Methods</h4>A frequency-matched case-control study included 1123 children and adolescents with obesity and 1231 controls from Guangzhou, China. Here, LEP is linked to obesity disorder.