We investigated the likely functional role of genes mapping closest to the lead SNPs using several sources of data, including human disease databases, evidence from animal models and bioinformatic analyses (see Box, Online Methods and Supplementary Table 4). The newly discovered and established glycemic loci represent various biological functions: signal transduction (DGKB/TMEM195, ADCY5, FADS1, ADRA2A, SLC2A2, GCK, GCKR, G6PC2, IGF1); cell proliferation and development (GLIS3, MADD, PROX1); glucose transport and sensing (SLC2A2, GCK, GCKR, G6PC2); and circadian rhythm regulation (MTNR1B, CRY2). All of these pathways represent further avenues for physiological characterization and possible therapeutic intervention. However, we note that other genes could be causal (Box and Supplementary Table 4) and further experimental evidence will be needed to link unequivocally specific genes with phenotypes.
