Journal
DIABETES CARE
Volume 41, Issue 11, Pages 2404-2413Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc18-0709
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Funding
- National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [R01-HL110400, R01-HL110380]
- National Institute of Diabetes and Digestive and Kidney Diseases through the Advanced Genomics and Genetics Core of the Diabetes Research Center at the Joslin Diabetes Center [P30-DK36836]
- NIH National Center for Advancing Translational Sciences [UL1TR001111]
- Alberta Innovates - Health Solutions
- McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care
- National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184]
- IAA [Y1-HC-9035, Y1-HC-1010]
- NIH, National Institute of Diabetes and Digestive and Kidney Diseases
- NIH, National Institute on Aging
- NIH, National Eye Institute
- Centers for Disease Control and Prevention
- General Clinical Research Centers and Clinical and Translational Science Awards
- Sanofi
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001111] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R44HL095181, R43HL095181, R01HL110380, R01HL110400] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK036836] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES103338] Funding Source: NIH RePORTER
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OBJECTIVEWe 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 METHODSA 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.RESULTSThe 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 x 10(-10), and HR per SD 1.35, 95% CI 1.16-1.58, P = 2 x 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 x 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.CONCLUSIONSWhen 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.
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