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Personalized Risk Prediction for Type 2 Diabetes: the Potential of Genetic Risk Scores

By Kristi Läll, Reedik Mägi, Andrew Morris, Andres Metspalu, Krista Fischer

Posted 29 Feb 2016
bioRxiv DOI: 10.1101/041731 (published DOI: 10.1038/gim.2016.103)

Purpose: The study aims to develop a Genetic Risk Score (GRS) for the prediction of Type 2 Diabetes (T2D) that could be used for risk assessment in general population. Methods: Using the results of genome-wide association studies, we develop a doubly-weighted GRS for the prediction of T2D risk, aiming to capture the effect of 1000 single nucleotide polymorphisms. The GRS is evaluated in the Estonian Biobank cohort (n=10273), analysing its effect on prevalent and incident T2D, while adjusting for other predictors. We assessed the effect of GRS on all-cause and cardiovascular mortality and its association with other T2D risk factors, and conducted the reclassification analysis. Results: The adjusted hazard for incident T2D is 1.90 (95% CI 1.48, 2.44) times higher and for cardiovascular mortality 1.27 (95% CI 1.10, 1.46) times higher in the highest GRS quintile compared to the rest of the cohort. No significant association between BMI and GRS is found in T2D-free individuals. Adding GRS to the prediction model for 5-year T2D risks results in continuous Net Reclassification Improvement of 0.26 (95% CI 0.15, 0.38). Conclusion: The proposed GRS would considerably improve the accuracy of T2D risk prediction when added to the set of predictors used so far. Keywords: genetic risk score, Type 2 Diabetes, risk prediction, genetic risk, precision medicine

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