Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms
- Jose M. de Miguel-Yanes, MD, MBA1,2,3,
- Peter Shrader, MS1,
- Michael J. Pencina, PHD4,
- Caroline S. Fox, MD, MPH2,5,
- Alisa K. Manning, MA6,
- Richard W. Grant, MD, MPH1,2,
- Josèe Dupuis, PHD5,6,
- Jose C. Florez, MD, PHD2,7,8,
- Ralph B. D'Agostino Sr, PHD4,5,
- L. Adrienne Cupples, PHD5,6,
- James B. Meigs, MD, MPH1,2,
- the MAGIC Investigators* and
- the DIAGRAM+ Investigators*
- 1General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts;
- 2Harvard Medical School, Boston, Massachusetts;
- 3Departamento de Medicina Interna, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;
- 4Department of Mathematics, Boston University, Boston, Massachusetts;
- 5National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts;
- 6Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts;
- 7Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts;
- 8Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
- Corresponding author: James B. Meigs, .
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.
↵*MAGIC and DIAGRAM+ Investigators are listed in supplementary Table A5 in the online appendix available at http://care.diabetesjournals.org/cgi/content/full/dc10-1265/DC1.
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- Received July 3, 2010.
- Accepted September 23, 2010.
- © 2011 by the American Diabetes Association.
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