The objective of the present study was to assess the association between individual genetic variants and haplotypes of several obesity-related genes (FTO, MC4R, MTCH2, NEGR1, SEC16B, INSIG2, TMEM18, KCTD15, SH2B1, FAIM2, ATXN2L, BDNF, BDNFOS, GNPDA2, ADRB2, PRL, PTER, ADIPOQ, ETV5, MAF, NPC1, CTNNBL1, and HTR2C) and BMI in two Spanish populations. This evidence concerns the gene SH2B1 and obesity due to melanocortin 4 receptor deficiency.