Pathway enrichment analyses applied to the 292 high-scoring prioritized genes implicate gene sets and pathways related to the central regulation of body weight (material and methods, Table S11), such as the neurotrophin signaling pathway44 (including BDNF, AKT3, RPS6KA5, MAP2K5, SH2B1, MAP3K3, BCL2, GSK3B, FOXO3, RAC1, and YWHAZ), which regulates appetite,45 and the PI3K/AKT pathway (including AKT3, FOXO3, GSK3A, GSK3B, MTOR, and YWHAZ),46 which is involved in central and peripheral appetite regulation and is implicated in the development of insulin resistance in peripheral tissues.47 The gene discussed is SH2B1; the disease is Insulin resistance.