Phenotype based risk models (the Framingham offspring and Cambridge risk scores) provided greater discrimination for type 2 diabetes than did models based on 20 common independently inherited alleles associated with risk of type 2 diabetes. The addition of 20 common genotypes associated with modest risk to phenotype based risk models produced only minimal improvement in the accuracy of risk estimation assessed by recalibration and at best a minor net reclassification improvement. The major translational application of the currently known common, small effect genetic variants influencing susceptibility to type 2 diabetes is likely to come from the insight they provide on causes of disease and potential therapeutic targets.
