Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population.
2010 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no 10, 2155-2162 p.Article in journal (Refereed) Published
AIMS/HYPOTHESIS: We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score. METHODS: Participants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test. RESULTS: Model 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 x 10(-20) vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 x 10(-6) vs null model), but lower discriminative power than model 1 (p = 5.92 x 10(-5)). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 x 10(-9)) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 x 10(-7) vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 x 10(-20)) and model 1 (p = 1.32 x 10(-5)); its ROC AUC was 0.626. CONCLUSIONS/INTERPRETATION: Adding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci.
Place, publisher, year, edition, pages
Springer , 2010. Vol. 53, no 10, 2155-2162 p.
Discriminative power, Genetic risk score, Glucose, Insulin, Lipids, Obesity, Polymorphism, Predictive power, Type 2 diabetes
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:umu:diva-36112DOI: 10.1007/s00125-010-1792-yPubMedID: 20571754OAI: oai:DiVA.org:umu-36112DiVA: diva2:351965