Importantly, 6/6 T2D risk alleles that significantly altered MPRA activity and in vivo islet chromatin accessibility (islet caQTL)7 did so in the same direction, and T2D SNP effects on MPRA activity were consistent with their previously reported effects on in vitro luciferase reporter activity, including rs7903146 (TCF7L2)6,66, rs1635852 (JAZF1)30, rs12189774 (VEGFA)67, rs2943656 (IRS1)7, and rs10428126 (IGF2BP2)7,68. This evidence concerns the gene IRS1 and type 2 diabetes mellitus.