Researchers weave deeper understanding of ancestry diversity and gene expression

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A new study published in Genetics of Nature by researchers from the Department of Biomedical Informatics (DBMI) at the University of Colorado School of Medicine, in partnership with the University of California, San Francisco and Stanford University, is the largest of its kind focusing on correlations of ancestry with biomedical traits and the first study to examine the role of genetic variants across diverse ancestors in the regulation of gene expression.

“We are trying to understand how genetic variability around the world allows us to gain a deeper understanding of the relationship between genetics and RNA levels and then protein levels and physiology,” says DBMI associate professor and co-author Study lead Chris Gignoux, PhD. . “The genome and gene expression, each on its own, tells us a lot. Having these layers attached helps us a lot more.”

Gignoux describes the genetic control of gene expression as a dial that controls the amount of the gene that is transcribed into RNA and protein levels, ultimately affecting function in various ways.

The study analyzed the whole genome and RNA sequencing of African American and Latino children. The researchers say their findings demonstrate the importance of measuring gene expression across multiple populations because those gene expressions can vary greatly by ancestry and enable new discoveries that may also reduce disparities in healthcare for historically underrepresented populations.

Gignoux’s lab used data from the Trans-Omics for Precision Medicine (TOPMed) consortium funded by the National Heart, Lung, and Blood Institute and the Population Architecture Study using Genomics and Epidemiology (PAGE) funded by the National Institute of Human Genome Research. They analyzed whole genome and RNA sequencing data from 2,733 African American and Hispanic/Latino children, exploring ancestry-related differences and heterozygosity in the genetic architecture of whole blood gene expression.

“The ultimate goal was for us to learn by looking at gene expression patterns in populations that came from the same ethnic group,” explains Gignoux. “People across Latin America do not reflect a homogeneous population, so that was part of the reason why it was important to not just look at Hispanics in a group, but to highlight what we can learn by studying Mexican Americans and Puerto Ricans. Specifically, we can take advantage of some of that diversity to understand some of these patterns.”

Because ethnicity is a sociopolitical identity, understanding the relationship between genetics and ancestry is quite complex and can vary greatly between individuals. This is true even within certain populations, such as people of Puerto Rican descent.

Historically, there has been a deficit in genetic research focused on people of non-European descent, but knowing more about the relationship between genetic variability and gene expression can inform more in-depth research on many different health issues.

That has been shown to be true in examples such as the medical community’s knowledge of heart attacks, which for decades only focused on men. With more research, it became clear that risk factors and symptoms look very different in women.

Without studying diverse populations, it is almost impossible to know that a disease might occur in another group of people. The work done by Gignoux and her research colleagues, including researchers from the various communities represented, may help inform more discoveries that are meaningful to diverse populations, as well as identify different risk factors faced by women with heart attacks.

“We’re not going to know what we don’t know unless we look, and that has the potential to affect how we think about people’s risk factors for a number of different conditions and traits,” says Gignoux. “It’s also important to look the right way and develop the methodologies so that we can take advantage of these types of diversity-focused efforts. The hope is that as these types of initiatives advance across genetic and non-genetic disciplines, there will be an opportunity to improve our understanding of biomedical traits for anyone entering the clinic.”