How diversity in genetic research can save lives
Our guest contributor Dr Neil Lamb continues his fortnighty Shareable Science Blog. Neil is the Vice President for Educational Outreach at the HudsonAlpha Institute for Biotechnology and Shareable Science will explore how genetics is relevant to people in their everyday lives.
In many ways, genetics boils down to a study of diversity. Humans share more than 99% of our DNA. More often than not, genetic researchers are most interested in the tiny pieces of the genome that differentiate us. Miniscule differences in our genetic code create the enormous spectrum of human life that we know and appreciate so deeply.
That said, the field of genetics is in desperate need of more diverse participation in research. To date, most studies have focused on European ancestries, and that narrow focus limits the potential impact of genetics for everyone, while actively excluding underrepresented groups from the progress being made.
Integrating more diversity in genetic research will literally save lives, so the issue begs for a complete understanding.
In 2015 #OscarsSoWhite began to trend because of the lack of diversity in the Academy Awards. Genetics also has a problem with diversity and inclusion, since most of the studies used to inform genetic research disproportionately rely on people with white European ancestry.
For example, genome-wide association studies (GWAS) are frequently used to associate genes with health outcomes. However many GWAS studies are skewed. As we pointed out in our guidebook that details the past year’s most important stories in genetics (p12), the most recent aggregations shows that nearly 88% of GWAS participants come from white European ancestry.
Different populations may have different combinations of genetic variants that contribute to a given disease. Because current GWAS studies rely on white people so heavily, the resulting conclusions focus on white people too, with limited application to other populations. This means you might find an earlier diagnosis or identify a specialized treatment if you have white European ancestry, while the same tests might miss that diagnosis or lead to ineffective treatment for people with other ancestral backgrounds.
It’s not just GWAS studies either; a lack of diversity also shows up in the human reference genome, which scientists use as a default genome for comparison purposes. It turns out that the “standard” reference genome leaves out millions of relevant base pairs. Research published in November 2018 found nearly 300 million base pairs that were present in people of African descent but not in the current standard reference genome.
To find genetic abnormalities, you have to start with a point of reference, and using a point of reference that reflects white European ancestry to the exclusion of other ancestral backgrounds does a disservice to underserved populations when it comes to medical applications of genetic knowledge.
These fundamental failures to reflect the world’s diversity have dire consequences for everyone.
Consequence for All
Diversifying genetic research will allow the field to more successfully address the needs of underrepresented populations, but it also adds to the overall knowledge bank that we all rely on for medical advancement.
For example, diverse populations have developed a cornucopia of genetic tools for battling disease. The guidebook gives one example:
[R]esearchers found some Americans of African descent had mutations on their PCSK9 genes that led to them having low levels of cholesterol in their bloodstream. Now PCSK9 inhibitors show promise as a way to lower cholesterol and heart disease risk across ancestries.
As humans evolved over the last 200,000 years and migrated around the world, genetic changes randomly arose within the various populations. Many provided benefits for surviving in new environments. Others had neutral or harmful impacts. Collectively, these differences make up the small, but important genetic diversity present across our family tree. We need an accurate picture of that global diversity if we hope to fully harness its meaning and benefit from its strength.
Of course, the underrepresented populations themselves also suffer for the lack of diversity in genetic research samples. For example, researchers in the Absher Lab at the HudsonAlpha Institute for Biotechnology recently started to reveal some of the reasons that lupus affects black women more frequently and severely than white women:
Distinctive epigenetic signatures of the disease are found in B cells, which are part of the immune system. The analysis performed by the Absher Lab revealed lupus-specific differences in methylation throughout B cell development between black and white women. Methylation changes can alter the degree to which a stretch of DNA functions without changing the genetic code itself. This research shows the most significant changes in methylation occur around genes related to Interferons, which are proteins that regulate immune response.These differences in B cell development could help explain the more severe symptoms and earlier age of onset for lupus in black women.
In the case of lupus, the differences in onset and severity of symptoms are well documented, so researchers are specifically looking for different mechanisms in black and white women. However there are many diseases and health outcomes that may look different on the genetic level for different populations, but we simply do not have the data available to know.
Our Best Efforts
While the lack of diversity in genetic research is a real and pervasive problem, there are aggressive steps being taken to counteract this dearth of information.
The National Institutes of Health laid the groundwork for its All of Us program in 2015. All of Us seeks to collect a million genetic samples across the United States, and the program has a particular emphasis on diversity. From the All of Us website:
Diversity in a research program is important for several reasons. First, where we live, how we live, and our background can all affect our health. Second, many groups of people have been left out of research in the past. This means researchers know less about their health.
By studying data from a diverse group of people, researchers can learn more about what makes people sick or keeps them healthy. What researchers learn could lead to better treatment and disease prevention for all of us. HudsonAlpha recently joined the All of Us initiative with an agreement to process thousands of samples using advanced long-read sequencing technology.
All of Us is part of a growing trend to actively seek out diverse samples in genetics. At the Institute alone, researchers are participating in the Alabama Genomic Health Initiative (AGHI) and SouthSeq, both of which aim to increase access to genetic information for underserved populations. The Institute’s campus even features a company, Acclinate Genetics, which is wholly dedicated to providing researchers with diverse sample sets.
The World’s Diversity Embraced
The human family is inextricably linked. At the core, our genetic recipes are nearly identical.
That tiny fraction of difference though…it defines the incredible diversity of our species. It is our duty to understand that diversity to the fullest extent we are capable. We all stand to benefit.
Catch up on the rest of the Shareable Science Series here.
The HudsonAlpha Institute for Biotechnology is a nonprofit institute in Huntsville, AL dedicated to developing and applying scientific advances to health, agriculture, learning, and commercialization. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a leader in genetics and genomics research and biotech education and fosters more than 40 diverse biotech companies on campus. To learn more, visit hudsonalpha.org.