Genetic Variants Associated With Cholesterol, Triglycerides

A global team of researchers, co-led by the University of Michigan School of Public Health, has discovered or confirmed 95 regions of the human ge­nome where genetic variants are associated with blood cholesterol and triglyceride levels, which are major indicators of heart disease risk. Of the total, 59 variants were associated with cholesterol and triglyceride lipid levels for the first time. The study is scheduled to appear in the journal Nature. Researchers look at 4 lipid traits: total cholesterol, low-density lipoprotein (LDL)-cholesterol, (the so-called bad cholesterol), high-density lipoprotein (HDL)-cholesterol (good cholesterol), and triglycerides. A combination of genetics and environment plays a role in determining those levels in our blood. Two of the regions identified in the study contain known drug targets, in addition to many loci not previously associated with lipid metabolism. Many of the common variants discovered by the study also are in or near genes known to have mutations associated with more ex­treme shifts in cholesterol or triglyceride levels. Further, many of the variants identified in these European-origin populations were shown to influence lipid traits across East Asian, South Asian, and African American populations as well. For these common variants in the ge­nome there seems to be a lot of similarity between different racial or ethnic groups in terms of their impact on lipid values and more generally on risk of disease. The research team is seeing similar multiethnic consistency of results for common variants in current work on type 2 diabetes. The similar findings across different an­cestry groups and the discovery of common variants in and near known lipid genes argues strongly against recent suggestions that these associations are due to the effects of rare variants much farther away in the genome. The majority of the variants identified as being associated with LDL-cholesterol are also associated with cardiovascular disease. Thus, these are now variants that are interesting in the context of LDL. People want their LDLs to be in a healthy range, but these variants are now also potentially predictive for cardiovascular events and potentially (therapeutic) targets for cardiovascular disease.