Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms

• Published in: Diabetes care Vol. 34; no. 1; pp. 121 - 125
• Main Authors: de Miguel-Yanes, Jose M, Shrader, Peter, Pencina, Michael J, Fox, Caroline S, Manning, Alisa K, Grant, Richard W, Dupuis, Josèe, Florez, Jose C, D'Agostino, Ralph B. Sr, Cupples, L. Adrienne, Meigs, James B
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2011
• Subjects: Adult; Age; alleles; Biological and medical sciences; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; elderly; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene loci; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic Predisposition to Disease - genetics; Genetic research; genetic variation; Genetics; Health risk assessment; Humans; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous; noninsulin-dependent diabetes mellitus; Odds Ratio; Original Research; people; Polymorphism, Single Nucleotide; Polymorphism, Single Nucleotide - genetics; prediction; Progeny; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reclassification; Regression analysis; Risk factors; Single-nucleotide polymorphism; Statistics; taxonomic revisions; Type 2 diabetes; Massachusetts; Endocrinopathy; Type 2 diabetes; Human; Genetic variability; Nutrition; Genotype; Metabolic diseases; Risk; Risk factor; Genetics; Single nucleotide polymorphism; Age; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc10-1265

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.