Validating the doubly weighted genetic risk score for the prediction of type 2 diabetes in the Lifelines and Estonian Biobank cohorts.
Abstract
As many cases of type 2 diabetes (T2D) are likely to remain undiagnosed, better tools for early detection of high-risk individuals are needed to prevent or postpone the disease. We investigated the value of the doubly weighted genetic risk score (dwGRS) for the prediction of incident T2D in the Lifelines and Estonian Biobank (EstBB) cohorts. The dwGRS uses an additional weight for each single nucleotide polymorphism in the risk score, to correct for "Winner's curse" bias in the effect size estimates. The traditional (single-weighted genetic risk score; swGRS) and dwGRS were calculated for participants in Lifelines (n = 12,018) and EstBB (n = 34,129). The dwGRS was found to have stronger association with incident T2D (hazard ratio [HR] = 1.26 [95% confidence interval: 1.10-1.43] and HR = 1.35 [1.28-1.42]) compared to the swGRS (HR = 1.21 [1.07-1.38] and HR = 1.25 [1.19-1.32]) in Lifelines and EstBB, respectively. Comparing the 5-year predicted risks from the models with and without the dwGRS, the continuous net reclassification index was 0.140 (0.034-0.243; p = .009 Lifelines), and 0.257 (0.194-0.319; p < 2 × 10-16 EstBB). The dwGRS provided incremental value to the T2D prediction model with established phenotypic predictors. It...Continue Reading
References
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Validity and reliability of self-reported diabetes in the Atherosclerosis Risk in Communities Study.
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