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Uncovering the Genetic Link Between Diabetes and Heart Disease

Uncovering the Genetic Link Between Diabetes and Heart Disease

September 2017

Type-2 diabetes (TD2) is a significant risk factor for coronary heart disease (CHD), and these two common conditions are leading causes of disease and death globally. But the biological pathways that explain the connection between them have remained somewhat murky, as have the causes of T2D. In a large analysis of genetic data, an international team led by researchers in the Perelman School of Medicine sought answers about what causes T2D and clarified how the two diseases are linked.

The researchers found evidence that, on the whole, the genetic link between the diseases appears to work in one direction: risk genes for T2D are much more likely to be associated with higher CHD risk than the other way around. And there also could be some pathways whereby pharmacological lowering of one disease increases the risk of the other. “Using evidence from human genetics, it should be possible to design drugs for type-2 diabetes that have either beneficial or neutral effects on CHD risk; however it is important to identify and further de-prioritize pathways that decrease the risk of type-2 diabetes but increase the risk of CHD," said co-first author Danish Saleheen, MBBS, PhD.

The scientists also found that diabetes-linked gene variants differ in their apparent effects on CHD risk, depending on their mechanisms. Variants that increase the chance of obesity or high blood pressure, for example, appear to boost CHD risk more strongly than do variants that alter insulin or glucose levels. Interestingly, this work identified dual diabetes-CHD risk loci that include targets of some existing drugs such as icosapent--an omega-3 fatty acid component of some fish oils, which lowers cholesterol and is sold in concentrated form as a prescription pharmaceutical.

Dr. Saleheen, co-senior author Benjamin F. Voight, PhD, an associate professor of Genetics, and their colleagues plan further investigations of the dual-risk genes they uncovered; and by studying people with related mutations, they hope to learn more about those genes' biology.

Authors: 

Wei Zhao, Asif Rasheed, Emmi Tikkanen, et al; Benjamin F. Voight and Danish Saleheen

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