The present study showed the participants with high PRS of appetite-related genes, mainly MC4R pathway-related genes, including SEC16B_ rs543874, BDNF_ rs6265 DNAJC27_ rs713586, MC4R_rs17782313, GIPR_ rs1444988703, increased the obesity risk by 1.6-fold. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.