INS and type 2 diabetes mellitus: The earliest exome array studies relevant to T2D were focused on glycemic traits; while some coding variants of moderate effect emerged from these studies (e.g., PAM for insulinogenic index [50], G6PC2 for fasting glucose [51, 52], and AKT2 for fasting insulin [53]), the number of significant associations was much smaller than would be expected from the hypotheses positing large contributions of rare variants to complex trait heritability.