SH2B1 and obesity due to melanocortin 4 receptor deficiency: So far, many of the GWAS hits have pointed to a role of the central nervous system (CNS) in obesity and have identified proven functional obesity genes such as MC4R, SH2B1 and BDNF. Disruption of Mc4r, Sh2b1 and Bdnf in mice all result in hyperphagia and/or obesity [5].