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

J. L. Vassy*, N. H. Durant, E. K. Kabagambe, M. R. Carnethon, L. J. Rasmussen-Torvik, M. Fornage, C. E. Lewis, D. S. Siscovick, J. B. Meigs

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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/m2 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.

Original languageEnglish (US)
Pages (from-to)2604-2612
Number of pages9
JournalDiabetologia
Volume55
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • Genetic susceptibility
  • Risk prediction
  • Type 2 diabetes
  • Young adults

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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