"We haven't figured out which variants are most active we've just noted that there are more signals than before." "When we figure out how all of these underlying genes function, then we'll be closer to understanding the contribution of genetic variation in lipid levels," Dr. They may also explain differences in lipid levels in the blood and in disease development. Investigators hope that these findings can help them better understand the underlying mechanisms of how DNA variants lead to changes in gene expression - when and which genes are turned on and off - and what genes do. These data suggest that some individual variants affect lipids only in certain populations, and not in others. Other results were more population-specific for example, the research team confirmed many strong signals at or near two genes, PCSK9 and APOA5. North notes that much remains to be understood about the heritability of lipid traits), the additional signals helped account for a larger amount of variation in lipid levels that can be explained by a person's genes.Īs a result, the scientists found an increase (1.3- to 1.8-fold) in the proportion of "phenotypic variation" - differences in lipid levels - that can be explained by genes in these groups, based on having many signals in the same place. While the investigators' search for the most influential gene variants is far from finished (Dr. That is, signals that are repeatedly found may indicate variants that are more likely to play a role in influencing blood lipids in all populations. Some signals were the same across these various populations, and the investigators were able to narrow the search for the most likely variants affecting lipid levels in the different groups of people. In East Asian subjects' genomes, they saw four locations with multiple signals. For example, the researchers found two or more signals at 10 locations in African American genomes, and in nine locations in European genomes, meaning at least two variants could be involved. In many cases, they found that lipid levels were affected by more than one variant in a particular genomic location. These loci were studied in 6,832 African Americans, 9,449 East Asians and 10,829 Europeans. In the study, investigators sought and analyzed associations, or signals, at 58 previously identified gene locations (called loci) known to be linked to lipid levels in the blood (LDL, HDL and triglycerides). North, and Karen Mohlke, Ph.D., associate professor of genetics at the University of North Carolina School of Medicine, along with their teams wanted to study ethnically diverse populations in an attempt to understand the total pool of potential candidate genes and genetic variants likely to affect blood lipids. However, many studies only examined groups from European ancestry. A person with high LDLs and triglycerides has a much higher risk for developing diseases affecting the cardiovascular system.Įarlier studies by other scientists had identified approximately 100 variants that were suspected to affect blood lipid levels. In several genomic regions, they identified two or more variants that influenced the amounts of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or triglycerides in the blood. They did this by examining thousands of gene variants in thousands of people of different ancestral backgrounds, focusing on DNA regions previously connected to blood lipid levels. The investigators linked gene variants in specific chromosomal regions to blood lipid levels. North and her team were supported by the National Human Genome Research Institute (NHGRI) Population Architecture Using Genetics and Epidemiology (PAGE) program ( ). "We hope that a better understanding of the genes and functional gene variants underlying blood lipid levels can help us figure out who might be at risk for high lipid levels, and better identify additional treatment targets," said Kari North, Ph.D., associate professor of epidemiology at the University of North Carolina School of Public Health, and a co-senior author on a paper describing the work that recently appeared in PLoS Genetics. They may also lead to new potential treatment strategies. The results may ultimately lead to new insights into how genes affect the development of unhealthy levels of cholesterol, and help explain differences in risks for heart disease. Combing regions of the genomes of more than 17,000 people from around the world, an international team of researchers has uncovered new evidence of potential genetic influences on blood lipid levels in three ethnic groups: African Americans, East Asians and Europeans.
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