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. 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. The shared genetic risk factors affect biological pathways including immunity, cell proliferation, and heart development.
The findings add to the basic scientific understanding of both these major diseases and point to potential targets for future drugs.
“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 study co-senior author Danish Saleheen, PhD, an assistant professor of Biostatistics and Epidemiology. “From a drug development perspective, it would make sense to focus on those pathways that are most strongly linked to both diseases,” Saleheen said.
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The researchers started by examining sets of genome data on more than 250,000 people, of South Asian, East Asian or European descent. In this large, multi-ethnic sample they were able to confirm most of the known diabetes “risk loci” — sites on the genome where small DNA variations have been linked to altered, usually higher, diabetes risk — and uncover 16 new ones.
With their analyses of the genome data, the scientists were also able to identify eight specific gene variants that are strongly linked to altered risk for both diseases. Seven of these gene variants, as expected, appeared to increase risk for both diseases.