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Diabetes Care. 2018 Nov;41(11):2404-2413. doi: 10.2337/dc18-0709. Epub 2018 Sep 27.

Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial.

Author information

1
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.
2
Department of Medicine, Harvard Medical School, Boston, MA.
3
Department of Pathology and Molecular Medicine and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
4
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
5
Bioinformatics Research Center and Department of Statistics, North Carolina State University, Raleigh, NC.
6
Departments of Medicine, Cardiac Sciences, and Community Health Sciences, Cumming School of Medicine, and Faculties of Medicine and Kinesiology, University of Calgary, Calgary, Alberta, Canada.
7
Department of Medicine, University of Washington, and Northwest Lipid Metabolism and Diabetes Research Laboratories, Seattle, WA.
8
Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
9
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
10
Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
11
Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
12
Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
13
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA alessandro.doria@joslin.harvard.edu.

Abstract

OBJECTIVE:

We evaluated whether the increasing number of genetic loci for coronary artery disease (CAD) identified in the general population could be used to predict the risk of major CAD events (MCE) among participants with type 2 diabetes at high cardiovascular risk.

RESEARCH DESIGN AND METHODS:

A weighted genetic risk score (GRS) derived from 204 variants representative of all the 160 CAD loci identified in the general population as of December 2017 was calculated in 5,360 and 1,931 white participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Outcome Reduction With Initial Glargine Intervention (ORIGIN) studies, respectively. The association between GRS and MCE (combining fatal CAD events, nonfatal myocardial infarction, and unstable angina) was assessed by Cox proportional hazards regression.

RESULTS:

The GRS was associated with MCE risk in both ACCORD and ORIGIN (hazard ratio [HR] per SD 1.27, 95% CI 1.18-1.37, P = 4 × 10-10, and HR per SD 1.35, 95% CI 1.16-1.58, P = 2 × 10-4, respectively). This association was independent from interventions tested in the trials and persisted, though attenuated, after adjustment for classic cardiovascular risk predictors. Adding the GRS to clinical predictors improved incident MCE risk classification (relative integrated discrimination improvement +8%, P = 7 × 10-4). The performance of this GRS was superior to that of GRS based on the smaller number of CAD loci available in previous years.

CONCLUSIONS:

When combined into a GRS, CAD loci identified in the general population are associated with CAD also in type 2 diabetes. This GRS provides a significant improvement in the ability to correctly predict future MCE, which may increase further with the discovery of new CAD loci.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00000620 NCT00069784.

PMID:
30262460
PMCID:
PMC6196830
DOI:
10.2337/dc18-0709
[Indexed for MEDLINE]
Free PMC Article

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