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Genetic Risk Factors for CVD in Type 1 Diabetes: the DCCT/EDIC Study

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posted on 22.04.2021, 16:24 by Ionut Bebu, Sareh Keshavarzi, Xiaoyu Gao, Barbara H. Braffett, Angelo J. Canty, William H. Herman, Trevor J. Orchard, Samuel Dagogo-Jack, David M. Nathan, John M. Lachin, Andrew D. Paterson
Background The role of genetic factors on the risk of cardiovascular disease (CVD) risk in type 1 diabetes remains unknown. We therefore examined whether previously identified genetic factors for coronary artery disease (CAD) are associated with the risk of CVD above and beyond established demographic and clinical factors in The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Methods Polygenic risk scores (PRS) and individual genetic variants identified in previous studies were obtained from genome-wide genotyping performed in 1371 DCCT/EDIC participants. Two composite CVD outcomes were considered: major adverse cardiovascular events (MACE) (CVD death or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Cox proportional hazards models assessed the association between the genetic factors and the risk of CVD when adjusted for other factors (including age, lipids, blood pressure and glycemia).

Results CAD PRS was strongly associated with the subsequent risk of any-CVD (42% and 38% higher risk per 1 standard deviation (SD) increase in unadjusted and fully adjusted models, respectively, p<0.0001), and with the risk of MACE (50% and 40% higher risk per 1SD increase in unadjusted and fully adjusted models, respectively, p<0.0001). Several individual SNPs were also nominally associated with the risk of any-CVD and MACE.

Conclusions Genetic factors are associated with the risk of subsequent cardiovascular disease in individuals with type 1 diabetes, above and beyond the effect of established risk factors such as age, lipids, blood pressure and glycemia.

Funding

The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA.

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