The former is clearly depicted in the higher odds ratios for rare PCSK1 protein truncating variants in the meta-analyses [40,41] and in a study combining rare heterozygous variants in the monogenic obesity genes leptin, leptin receptor, POMC, and PCSK1, where they found a higher BMI for subjects with high-impact heterozygous variants [14]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.