In the study including 2386 individuals, De et al. analyzed interactions between twelve genetic variants robustly associated with obesity (BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18). Here, MTCH2 is linked to obesity due to melanocortin 4 receptor deficiency.