Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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, ; DIAGRAM+ Investigators,

Published Date

  • January 2011

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 121 - 125

PubMed ID

  • 20889853

Pubmed Central ID

  • 20889853

Electronic International Standard Serial Number (EISSN)

  • 1935-5548

Digital Object Identifier (DOI)

  • 10.2337/dc10-1265

Language

  • eng

Conference Location

  • United States