de Miguel-Yanes, Jose M.Shrader, PeterPencina, Michael J.Dupuis, JosèeD'Agostino, Ralph B.Cupples, L. AdrienneFox, CarolineManning, AlisaGrant, Richard WilliamFlorez, JoseMeigs, James2012-08-072011de Miguel-Yanes, Jose M., Peter Shrader, Michael J. Pencina, Caroline S. Fox, Alisa K. Manning, Richard W. Grant, Josèe Dupuis, et al. 2011. Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms. Diabetes Care 34(1): 121-125.0149-5992http://nrs.harvard.edu/urn-3:HUL.InstRepos:9368045OBJECTIVE: 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.en-USepidemiologyhealth services researchJournal Article2012-08-0710.2337/dc10-1265