Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish populationReport as inadecuate




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Diabetologia

, Volume 53, Issue 10, pp 2155–2162

First Online: 23 June 2010Received: 18 January 2010Accepted: 13 April 2010

Abstract

Aims-hypothesisWe determined whether single nucleotide polymorphisms SNPs previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score.

MethodsParticipants 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.

ResultsModel 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 p < 1.00 × 10 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 × 10 vs null model, but lower discriminative power than model 1 p = 5.92 × 10. Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model ROC AUC 0.565; p = 1.44 × 10 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 × 10 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 × 10 and model 1 p = 1.32 × 10; its ROC AUC was 0.626.

Conclusions-interpretationAdding 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.

KeywordsDiscriminative power Genetic risk score Glucose Insulin Lipids Obesity Polymorphism Predictive power Type 2 diabetes AbbreviationsDIAGRAMDiabetes Genetics Replication and Meta-Analysis

GRSGenetic risk score

NSHDSNorthern Sweden Health and Disease Study

ROC AUCArea under the receiver operator characteristic curve

SNPSingle nucleotide polymorphism

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Author: B. Fontaine-Bisson - F. Renström - O. Rolandsson - The MAGIC investigators - F. Payne - G. Hallmans - I. Barroso - P. W. 

Source: https://link.springer.com/



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