Our framework not only identified key regulators which have been previously reported for known off-target effects of statins, such as E2F1 and POU2F1 for systemic lupus erythematosus and JUN and NFKB1 for anti-cancer-related pathways, but also novel regulators (FOXD1/2, PATZ1, and TLX2) that may play important roles in statin-increased risk for Type II diabetes mellitus (T2DM). Here, POU2F1 is linked to type 2 diabetes mellitus.