When it comes to learning how to prevent heart disease, including diverse populations isn't just the right thing to do, it also makes the science better.

A new paper examined genes behind blood cholesterol levels for more than 1.5 million people in order to learn more about who might be likely to develop this important risk factor. But unlike genetic research of the past that typically focused on people with European ancestry, this one included genome-wide studies of 350,000 participants with African, Hispanic, East Asian or South Asian ancestry.

The study found that genetic variants related to LDL cholesterol, the so-called "bad" cholesterol that can lead to blocked vessels, were mostly similar for all participants. However, a few unique variants came to light when comparing results across population groups.

Researchers said studying samples from a wide variety of ancestry groups helped find the causal genes more quickly. And since this type of genetic study can aid in the prediction of people who will develop high cholesterol and heart disease later in life, including individuals of different ancestries, helps ensure that people of diverse ancestries will be able to benefit from prevention strategies.

Improving cardiovascular risk for everyone

Last author Cristen Willer, Ph.D., said these new findings will allow scientists to predict future high cholesterol levels as well in people with African ancestry as they can in people with European ancestry.

"The large sample size, diversity of the study population and large role of genetics on lipid levels make this study one of the first to truly evaluate genetic prediction in different ancestries at this scale," Willer said. "We hope this sets a precedent for future genetic studies to ensure the research benefits global populations and helps as many people as possible."

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Willer, a professor of internal medicine, human genetics and computational medicine and bioinformatics at University of Michigan Health, lead author Sarah Graham, Ph.D., a postdoctoral researcher in the Willer Lab, and co-senior author Themistocles (Tim) L. Assimes, M.D., Ph.D., from Stanford University and the Palo Alto VA Hospital, and the rest of the team published their findings in Nature.

The researchers performed a meta-analysis for this study using huge amounts of data from the Global Lipids Genetics Consortium (GLGC) where Willer is a lead investigator.

The consortium brings together genome-wide association data from 200 cohort studies across the globe, allowing research teams to closely investigate key genetic variation related to blood cholesterol levels in a lot of people at once. U.S. veterans participating in the Million Veteran Program were a major contributor to the increased diversity of the GLGC. In all, around 500 scientists who have collected and analyzed these data are credited as co-authors.

Large, diverse samples in health research lead to large, broad impact

The researchers already knew they needed many, many participants in order to draw big conclusions about lipid levels. What they didn't know in advance was exactly how big the benefit would be of studying diverse samples.

Of three aspects of the research they examined, diversity made a big difference for two of them, and a smaller difference for the third. Willer said they identified approximately the same number of total genetic variation related to lipids (thousands of them), irrespective of the level of diversity.

However, for homing in on the functional gene, or for predicting high cholesterol levels, researchers report that diversity was critically important.

"We find that increasing the diversity of the populations studied rather than simply increasing sample size more efficiently identifies the genetic variants that control cholesterol levels in our blood," Assimes said. "Importantly, we can potentially level the playing field when it comes to predicting cholesterol levels if we introduce diversity into our study design, and the more diversity we introduce, the better."

Identifying lipid concerns earlier

LDL cholesterol is a warning bell for future cardiovascular events like heart attacks, so a high cholesterol level in an annual physical is likely to lead to a discussion about how to lower it.

If you could find out in advance that you were more susceptible to having high blood lipids, or high risk of heart attacks, then you could reduce your cholesterol before it even becomes a problem, Graham said.

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"We hope this study will one day allow physicians to better identify people at risk of high cholesterol and cardiovascular disease who may benefit from lifestyle changes or lipid-lowering medication earlier in life," she added.

This study also suggests that genetic studies of any diseases would likely benefit from studying people of diverse ancestries, researchers said.

"We should work hard to ensure that genetics research benefits all people, and improving diversity of ancestries represented in research is an important step towards equality," Willer said.

Paper cited: "The power of genetic diversity in genome-wide association studies of lipids," Nature. DOI: 10.1038/d41586-021-02998-2