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Multicenter Study
. 2012 Oct;55(10):2604-2612.
doi: 10.1007/s00125-012-2637-7. Epub 2012 Jul 11.

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study

J L Vassy  1   2 , N H Durant  3 , E K Kabagambe  4 , M R Carnethon  5 , L J Rasmussen-Torvik  5 , M Fornage  6 , C E Lewis  7 , D S Siscovick  8 , J B Meigs  9   10
Affiliations
Multicenter Study

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study

J L Vassy et al. Diabetologia. 2012 Oct.

Abstract

Aims/hypothesis: Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone.

Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood. We used Cox regression to build nested prediction models for incident type 2 diabetes based on clinical risk factors assessed in young adulthood (age, sex, race, parental history of diabetes, BMI, mean arterial pressure, fasting glucose, HDL-cholesterol and triacylglyercol), without and with a 38-variant genotype score. Models were compared with C statistics and continuous net reclassification improvement indices (NRI).

Results: Of 2,439 participants, 830 (34%) were black and 249 (10%) had a BMI ≥ 30 kg/m(2) at baseline. Over a mean 23.9 years of follow-up, 215 (8.8%) participants developed type 2 diabetes. The genotype score significantly predicted incident diabetes in all models, with an HR of 1.08 per risk allele (95% CI 1.04, 1.13) in the full model. The addition of the score to the full model modestly improved reclassification (continuous NRI 0.285; 95% CI 0.126, 0.433) but not discrimination (C statistics 0.824 and 0.829 in full models with and without score). Race-stratified analyses were similar.

Conclusions/interpretation: Knowledge of genotype predicts type 2 diabetes over 25 years in white and black young adults but may not improve prediction over routine clinical measurements.

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Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
Incident type 2 diabetes (T2DM) in the CARDIA study. Cumulative incidence of time to detection of type 2 diabetes, stratified by tertiles of genotype risk score (a) and BMI (b). Dotted line, highest tertile; dashed line, middle tertile; solid line, lowest tertile
See this image and copyright information in PMC

Comment in

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