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Diabetes Care. 2011 Jan;34(1):121-5. doi: 10.2337/dc10-1265. Epub 2010 Oct 1.

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

Author information

1
General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

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.

PMID:
20889853
PMCID:
PMC3005447
DOI:
10.2337/dc10-1265
[Indexed for MEDLINE]
Free PMC Article

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