Persons with severe obesity were stratified into either metabolically healthy (Met-H) or metabolically challenged (Met-C) groups according to well-established clinical parameters including markers of glucose dysmetabolism (e.g. glucose, insulin, HOMA-IR) and hepatocellular disease (e.g. NAFLD activity score (NAS), aspartate transaminase (AST), ALT, and gamma-glutamyltransferase (GGT); Fig. 7e–h; Supplementary Table 7). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.