INS and obesity due to melanocortin 4 receptor deficiency: Fig. 2 shows one of L-SSMD gene sets, G-protein coupled receptor activity, which contains 94 genes. In addition, eight GWAS catalog gene sets showed relatively large SSMD (P < 0.001, permutation test), though not significant following Bonferroni correction. These sets included genes implicated in adverse responses to chemotherapy, conduct disorder, fasting insulin-related traits, metabolite levels, obesity, retinal vascular caliber, temperament, or thyroid hormone levels (S1Table).