Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms
de Miguel-Yanes, Jose M.
Pencina, Michael J.
D'Agostino, Ralph B.
Cupples, L. Adrienne
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Citationde 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.
AbstractOBJECTIVE: 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.
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