Researchers decreased the number of genetic variations substantially related with blood lipid levels and established a polygenic risk score to predict elevated low-density lipoprotein cholesterol levels, a major risk factor for heart disease, in a large-scale investigation of persons of various ancestries.
The Global Lipids Genetics Consortium led the study, which was published in the journal Nature. Researchers from the National Human Genome Research Institute (NHGRI), which is part of the National Institutes of Health, are among the authors.
Lipids are fat-like molecules found in the blood and tissues of the body. Cholesterol and triglycerides are the two main types. Although the body requires a specific quantity of lipids for regular operation, high lipid levels can raise the chance of having a heart problem.
Polygenic risk scores are based on DNA alterations linked to specific diseases and provide an assessment of an individual’s risk for such diseases.
“Finding the set of genomic variants that are important for this trait is key for us to understand the biology and identify new drug targets,” said Cristen Willer, Ph.D., senior author, and professor of human genetics at the University of Michigan, Ann Arbor. “These genomic variants then inform how well polygenic risk scores work to determine risk for such diseases.”
The message couldn’t be more clear. To have a fuller understanding of the effects of genomic variation on disease, we simply must include as many diverse groups of people as possible. It is the single biggest way by which we can ensure that the gains of genomic medicine and technologies are equitably deployed to serve the health needs of all human populations.
Rotimi
The genomics community has conducted over 6,000 research looking at the link between individual genetic variations and cardiovascular disease since the field’s start. However, individuals from European ancestral groups were overwhelmingly included in the design of these investigations.
To solve this problem, scientists compiled data from 201 previous genome-wide association studies, which included approximately 1.65 million people from five ancestral groups: African, East Asian, European, Hispanic, and South Asian.
A total of 1.32 million of the studies were of European origin, with the remaining 350,000 being of non-European heritage. The research gave information on cholesterol and triglyceride levels in the blood.
The polygenic risk scores were generated using data from each of the different ancestral groups, either separately or all together, by the research team. The risk scores were then examined in a variety of investigations, including Africans enrolled in the Africa America Diabetes Mellitus research from Ghana, Kenya, and Nigeria. The study’s lead investigator was Charles Rotimi, Ph.D., scientific director of the NHGRI Intramural Research Program.
The findings revealed that a polygenic risk score incorporating various genomic data is far more predictive of whether a person of any ancestry will have elevated low-density lipoprotein cholesterol levels than a score based solely on European genomic data.
“The message couldn’t be more clear. To have a fuller understanding of the effects of genomic variation on disease, we simply must include as many diverse groups of people as possible,” said Rotimi, a co-author on the paper.
“It is the single biggest way by which we can ensure that the gains of genomic medicine and technologies are equitably deployed to serve the health needs of all human populations.”
The polygenic risk score that used data from all ancestries performed at least as well as or better than risk scores created from data from the same ancestral group for each ancestral group.
“These results show that our concerted effort to include many diverse groups of people in genomic research will yield benefits such as new therapeutics and prevention strategies that improve the health of all people,” says Cashell Jaquish, Ph.D., a genetic epidemiologist and program officer within the Division of Cardiovascular Sciences at the National Heart Lung, and Blood Institute.
Funding for the study was provided by the National Heart, Lung and Blood Institute, part of the National Institutes of Health.
