Because part of the information included in the family history component of a risk score will reflect common genotypes, this may have undermined the incremental value of genetic information for risk prediction. However, the variants we studied explain only a small proportion of the familial aggregation of diabetes.36 Whether genotypes have greater predictive utility in particular categories of patient (such as among leaner people or those of a particular ancestry) could be assessed by pooling participant level data from a large number of prospective studies with the relevant information to ensure adequate power. Our current analysis is limited to the 20 common risk alleles for type 2 diabetes identified by large association or genome-wide studies. However, sequence variants of intermediate frequency but larger effect size are likely to be uncovered by future research, so our interpretation on the predictive utility of genotype should be regarded as interim. Moreover, as the actual causal variants at each gene/region remain for the most part uncertain, the predictive utility of genetic markers may also have been underestimated.
