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Diabetologia. 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.

Author information

1
General Medicine Division, Massachusetts General Hospital, 50 Staniford Street, 9th floor, Boston, MA, 02114, USA. jvassy@partners.org.
2
Department of Medicine, Harvard Medical School, Boston, MA, USA. jvassy@partners.org.
3
Division of Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Alabama Birmingham School of Medicine, Birmingham, AL, USA.
4
Department of Epidemiology, University of Alabama Birmingham School of Public Health, Birmingham, AL, USA.
5
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
6
Institute of Molecular Medicine Research Center for Human Genetics, The University of Texas Health Science Center, Houston, TX, USA.
7
Division of Preventive Medicine, Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA.
8
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.
9
General Medicine Division, Massachusetts General Hospital, 50 Staniford Street, 9th floor, Boston, MA, 02114, USA.
10
Department of Medicine, Harvard Medical School, Boston, MA, USA.

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.

PMID:
22782289
PMCID:
PMC3434294
DOI:
10.1007/s00125-012-2637-7
[Indexed for MEDLINE]
Free PMC Article
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