AbstractCirculating levels of leptin and adiponectin are closely associated with obesity. However, it is not known whether there are common shared genes or environment exerting influences on the levels of leptin, adiponectin, and BMI. We aimed to assess the relative contribution of genes and environment to adiponectin, leptin, and BMI individually as well as simultaneously to the three measures. Our subjects included a total of 228 twin/sibling pairs aged 12 to 18 (130 monozygotic twins, 68 dizygotic twins and 30 sibling pairs) were recruited from the middle schools. Multivariate analyses were applied to twin/sibling data using structural equation modeling. The results showed that intraclass correlations for adiponectin, leptin and BMI were higher in the MZ twins than those in the DZ/SP group. The relative contribution of genes to adiponectin (39%) was comparable to those of shared environment (40%). In contrast, leptin and BMI were influenced mostly by genes (74% and 89%, respectively). The multivariate genetic analyses showed that a latent factor underlying the three measures was identified, with BMI being equivalent to this latent factor. The BMI-dependent genetic factor explains only 15% and 34% of variation of adiponectin and leptin, respectively. These data indicate a differential contribution of genetic factors for the variation of adiponectin, leptin and BMI. More importantly, only a small portion of the genetic influences on adiponectin and leptin was attributed to BMI. Our findings provided more insight into the complex regulation of adiponectin and leptin in obesity.