Although associated variants typically implicate genomic regions rather than individual genes, we note that some of the 32 loci include candidate genes with established connections to obesity. Several of the 10 previously identified loci are located in or near genes that encode neuronal regulators of appetite or energy balance, including MC4R12,25, BDNF26, and SH2B111,27. Each of these genes has been tied to obesity, not only in animal models, but also by rare human variants that disrupt each of these genes and lead to severe obesity24,28,29. Using the automated literature search programme, Snipper (Online Methods), we identified various genes within the novel loci with potential biological links to obesity-susceptibility (Supplementary Note). Among the novel loci, the location of rs713586 near POMC provides further support for a role of neuroendocrine circuits that regulate energy balance in susceptibility to obesity. POMC encodes several polypeptides including α-MSH, a ligand of the MC4R gene product30, and rare mutations in POMC also cause human obesity23,29,31.
