Thus, investigators are fundamentally challenged to (i) screen and identify relevant candidates in vivo, (ii) determine if loss- or gain-of-function underlies the association, (iii) link perturbed gene function to hallmark type 2 diabetes mellitus physiological phenotypes like insulin production or secretion, and (iv) identify relevant tissue(s) where the biological function of a specific regulator is required. Here, INS is linked to diabetes mellitus.