The SH2B1 gene is for instance an interesting candidate as SNPs at the SH2B1 locus are associated with BMI by GWAS [8], rare deletions including SH2B1 are associated with a Mendelian form of obesity [9, 10] and inactivation of SH2B1 in mice leads to hyperphagia, leptin resistance and obesity [11]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.