Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms

OBJECTIVE- To test if knowledge of type 2 diabetes genetic variants improves disease prediction. RESEARCH DESIGN AND METHODS- We tested 40 single nucleotide polymorphisms (SNPs) associated with diabetes in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (<50 years, diabetes cases = 144; or >= 50 years, diabetes cases = 302). Models included clinical risk factors and a 40-SNP weighted genetic risk score. RESULTS- In people <50 years of age, the clinical risk factors model C-statistic was 0.908; the 40-SNP score increased it to 0.911 (P = 0.3; net reclassification improvement (NRI): 10.2%, P = 0.001). In people >= 50 years of age, the C-statistics without and with the score were 0.883 and 0.884 (P = 0.2; NRI: 0.4%). The risk per risk allele was higher in people <50 than >= 50 years of age (24 vs. 11%; P value for age interaction = 0.02). CONCLUSIONS- Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people.