Second, three ‘tier 3’ genes (SIX3, HESX1, GHRL) had strongly suggestive evidence of association in ProDiGY despite showing no evidence of association for adult-onset T2D (all had P > 0.69 in AMP-T2D-GENES) and no previous links to monogenic diabetes. This evidence concerns the gene HESX1 and type 2 diabetes mellitus.