Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms.
OBJECTIVE
To test if knowledge of type 2 diabetes genetic variants improves disease prediction.


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.
de Miguel-Yanes
Jose M
JM
General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Shrader
Peter
P
Pencina
Michael J
MJ
Fox
Caroline S
CS
Manning
Alisa K
AK
Grant
Richard W
RW
Dupuis
Josèe
J
Florez
Jose C
JC
D'Agostino
Ralph B
RB
Cupples
L Adrienne
LA
Meigs
James B
JB
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*