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 2010 ; 34: 121-5.
de Miguel-Yanes JM, Shrader P, Pencina MJ, Fox CS, Manning AK, Grant RW, Dupuis J, Florez JC, D'Agostino RB, Cupples LA, Meigs JB, MAGIC Investigators MAGIC Investigators, and DIAGRAM+Consortium
DOI : 10.2337/dc10-1265
PubMed ID : 20889853
PMCID : PMC3005447
To test if knowledge of type 2 diabetes genetic variants improves disease prediction.
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.
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).
Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people.