Researchers have been scouring the human genome for variants that can be linked with susceptibility to coronary heart disease. Lipids—such as cholesterol and triglycerides—are known determinants of the disease and though their levels are often tied to lifestyle factors such as diet, the tendency to develop high blood lipid levels can be inherited.
Using genetic information from more than 27,000 people, drawn from their own and two other genome-wide association studies, Sekar Kathiresan, an HMS instructor in medicine at Massachusetts General Hospital, and colleagues report in the February Nature Genetics that they have identified 18 loci containing variants that correlate with blood lipid levels in humans, six of which had not been discovered in previous associations.
The lipid-associated genetic variants look like they may also correlate with risk of heart disease. A previous study published by a British research group last year showed that variants within specific regions of the genome directly correlated with susceptibility to coronary heart disease. What their study had not shown, however, was a link between these variants and cholesterol, a leading risk factor for the disease.
Interestingly, another study published in the February Nature Genetics demonstrates that there is some common ground between lipid-associated variants and variants previously linked with susceptibility to heart disease. “We were really excited to see that one of the genetic variants we found to be associated with cholesterol levels, was also linked to heart disease by the British group,” said Kathiresan.
“This is a significant development,” he said. “Previous studies looking for genetic loci underlying cardiovascular traits have used far smaller group sizes, which inevitably made the discovery process very slow. The great thing about our study was that instead of competing with other groups, we actually joined forces, which helped us to uncover many new genetic regions related to lipid levels.”
While these are promising findings, there is still a lot of work to do. As Kathiresan points out: “Each of these regions individually has a very modest impact on lipid levels, and it is only when they are looked at in combination that they have a significant correlation with cardiovascular disease or disease traits.” Kathiresan and his group at the Broad Institute are now performing studies to both extend and refine these results to isolate specific genes linked to lipid levels and susceptibility to heart disease.
“A clearer understanding of the genetic underpinnings of cardiovascular traits will have a huge impact on medical advancement” said Kathiresan. “It will not only further our knowledge of disease mechanisms but will also provide us with new targets for future drug therapies. It may even enable us to produce clinical diagnostic tests to identify vulnerable individuals early and to treat them before the disease takes hold.”
