In conclusion, in this study, we determined that STAT3, CORO1C, SERPINH1, MVP, ITGB5, PCM1, SIRT1, EEF1G, PTEN and RPS2 might be critical genes in the development and prognosis of obesity through bioinformatics analysis combined with validations. This evidence concerns the gene RPS2 and obesity due to melanocortin 4 receptor deficiency.