CHOP Tool Help Link Genes to Cholesterol

In the largest-ever genetic study of cholesterol and other blood lipids, an international consortium has identified 21 new gene variants associated with risks of heart disease and metabolic disorders. The findings expand the list of potential targets for drugs and other treatments for lipid-related cardiovascular disease, one of the world's leading causes of death and disability.

In its study, the International IBC Lipid Genetics Consortium used the Cardiochip, a gene analysis tool invented by Brendan J. Keating, PhD, lead clinical data analyst at the Center for Applied Genomics. Since Dr. Keating created the Cardiochip in 2006, researchers have used it to pinpoint gene variants in dozens of studies. The device contains approximately 50,000 DNA markers across 2000 genes implicated in cardiovascular disease.

Comprising over 180 researchers, the international consortium analyzed genetic data from over 90,000 individuals of European ancestry. First the researchers used the Cardiochip in a discovery dataset of over 65,000 individuals from 32 previous studies. They then sought independent replication in other studies covering over 25,000 individuals, as well as in a previously reported study of 100,000 individuals.

From this meta-analysis, the consortium identified 21 novel genes associated with levels of low-density lipoproteins (LDL, or "bad cholesterol"), high-density lipoproteins (HDL, "good cholesterol"), total cholesterol (TC), and triglycerides (TG), as well as verifying 49 known signals. The researchers also found that some of the strongest signals appeared to be gender-specific—some variants were more likely to appear in men, others in women.

The consortium plans to follow this published work with a project to identify which of the loci reported directly cause disease, and how this knowledge can help in the development of novel drugs. The consortium will also devote its significant pooled resources to identifying interactions among genetic polymorphisms (single-base variations in DNA) and biological markers of downstream cardiovascular disease.