The minor allele frequency of rs566629828 is at the lower end of common variations (MAF = 0.0147) and has one of the largest effects on weight (β^=0.22) and BMI (β^=0.27) reported so far, with the exception of extremely rare variants directly implicated in lipid metabolism.24 For comparison, genetic variants in other well-characterized genes associated with obesity, i.e., PCSK1 and MC4R, have comparable effect sizes in the general population. The gene discussed is MC4R; the disease is obesity due to melanocortin 4 receptor deficiency.