These synthetic approaches allowed for successful detection of  CDKN2B and TCF7L2 interacting effect for T2D risk and CDKN2B and  JAZF1 interacting effect on TG/HDL ratio increase over time among  T2D families in the FHS. These interacting effects were consistent  in conferring risk of T2D or progressive insulin resistance with  modest effect sizes. The gene discussed is CDKN2B; the disease is type 2 diabetes mellitus.