GCG and obesity due to melanocortin 4 receptor deficiency: Though it remains to be demonstrated that the genes at which the index SNPs are located in are functionally responsible for the GWAS signals for obesity and T2D, there is a great amount of evidence supporting the roles of the identified genes, particularly for THADA and PAX4. The THADA risk allele is linked to decreased glucagon-like peptide-1-induced and arginine-induced insulin release [35], while studies have shown that the early expression of PAX4 is involved in the differentiation of β-cells in the pancreas, thus affecting insulin secretion [36], [37].