Type 2 diabetes (T2D) has become a global epidemic affecting more than 380 million people worldwide; yet there are knowledge gaps in understanding the etiology of type-2 diabetes.
It is also a significant risk factor for coronary heart disease (CHD), but the biological pathways that explain the connection have remained somewhat murky.
In an analysis of genetic data, published in the journal Nature Genetics, researchers from University of Pennsylvania in the US, looked into what causes type 2 diabetes.
Examining genome sequence information for more than 250,000 people, the researchers first uncovered 16 new diabetes genetic risk factors, and one new CHD genetic risk factor; hence providing novel insights about the mechanisms of the two diseases.
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They then showed that most of the sites on the genome known to be associated with higher diabetes risk are also associated with higher CHD risk.
For eight of these sites, the researchers were able to identify a specific gene variant that influences risk for both diseases.
"Identifying these gene variants linked to both type 2 diabetes and CHD risk in principle opens up opportunities to lower the risk of both outcomes with a single drug," said Danish Saleheen, assistant professor at University of Pennsylvania.
"From a drug development perspective, it would make sense to focus on those pathways that are most strongly linked to both diseases," Saleheen said.
The researchers started by examining sets of genome data on more than 250,000 people, of South Asian, East Asian or European descent.
They were able to confirm most of the known diabetes risk sites on the genome - and uncover 16 new ones.
Seven of these gene variants, as expected, appeared to increase risk for both diseases.
The eighth, a variant of the gene for the cholesterol- transport protein ApoE, is associated with higher diabetes risk but lower CHD risk - a finding that is somewhat puzzling, Saleheen said.
However, it is consistent with data from statin trials showing that pharmacologically lowering LDL cholesterol can modestly increase diabetes risk.
The researchers also hope to learn more about the biology of the newly discovered dual-risk genes by studying people who have mutations in those genes.