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

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

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • African Continental Ancestry Group / genetics
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Follow-Up Studies
  • Genotype*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • United States
  • Young Adult