Genomic Equity, a Public Health Imperative

written by Jennifer Troyer, Former Director, Division of Extramural Operations, National Human Genome Research Institute (NIH), in her personal capacity

When 27 UNIHTED asked if anyone wanted to do a post on scientific advancement for National PHC in honor of National Public Health Week, I immediately said, “I could do one on equity in genomics.” Now I sit here wondering what I have gotten myself into. What can I say that can adequately express the current state of affairs? How do I explain how far we have come on this issue, how far we have yet to go, and the damage being done by recent attacks from the current administration on diversity, equity, and inclusion in science? These attacks have derailed not just social justice goals, but also our ability to advance science in ways that will lead to better public health for everyone.

Both similarity and differences can come with imposed societal value and judgement, and the science of genomics can intentionally or inadvertently be used to amplify societal inequities.

One of the casualties of the DOGE-led destruction of the federal workforce was the National Human Genome Research Institute (NHGRI) History of Genomics Program. This program was instituted as a guiding light for the nascent but growing field of genomics to ensure that, along with appreciating the scientific advancements that had been made, we did not repeat the mistakes of the past and allow genomics to be used as a tool for division or increased inequity. To me, the beauty and the fascination of genomics has always been the underlying simplicity of the code that unites all life and at the same time the multitude of possible combinations of those 4 simple letters that creates endless variation and diversity. We are all amazingly similar and wonderfully unique at the same time. However, both similarity and differences can come with imposed societal value and judgement, and the science of genomics can intentionally or inadvertently be used to amplify societal inequities. For more insight on the intentional transgressions, please visit the site above (while it still exists, since NHGRI communication staff have all been fired).* I will attempt to address some of the structural ones below.

In the beginning, most human genomic data came from people of European descent for two major reasons, one sociological and one technical. The sociological reason was that genomics was an expensive academic pursuit and the majority of academic institutions that could afford the expensive equipment and reagents had primarily faculty of European descent and served communities similar to themselves. The technological reason was that it was harder to produce clean sequence data from highly heterozygous samples (i.e., samples with significant variation between the chromosomes inherited from their mother and their father); the higher the heterozygosity, the worse the technology performed. People with more recent African ancestry have higher heterozygosity because of the longer evolutionary history of their chromosomes with historically southern African populations tending to have the highest levels of heterozygosity; those of primarily European ancestry went through population bottlenecks more recently, so have higher homozygosity, or similarity between their two chromosomes. European-ancestry chromosomes also have longer tracts of linkage disequilibrium (LD; sets of variants that travel together on a chromosome) because they have had less time for the process of recombination to re-arrange the variation. Once these simpler genomes were sequenced, they became the gold standard references for all subsequent work. The result has been that despite all the sequencing that has been done over the last 30 years, the majority of it was from people of European ancestry and all others have been compared to the original reference genomes which are missing diversity, so most genomic databases are still missing a majority of the variation in human genomes.

Genome in 3-D Credit: Darryl Leja and Ernesto Del Aguila III, NHGRI

Ironically, it turns out that highly heterozygous genomes with shorter tracts of LD can be much more informative for discovering the genetic bases of disease. Therefore in missing variation, we are also missing valuable tools for scientific discovery. Over the last 15 years, many programs at NIH and elsewhere have been focused on increasing the representation of diverse genomes and making progress towards decreasing the inequity in genomic data and increasing the informational value of these datasets. NIH programs included H3Africa, TopMed, eMERGE, PRIMED, and the Human Pangenome Reference project, among many others. Unfortunately, as more and more European-ancestry genomes continue to be sequenced as well, it is hard to catch up and the gap still exists. The gutting of all things “diversity” focused at NIH puts many of these efforts in danger of being derailed or at least diluted.

So, why does this matter for public health? The cost of genomics has decreased significantly, making it more accessible; it has also proven effective as a diagnostic for many conditions. In some ways, genomics is becoming a standard of care in much of the developed world and the developing world may not be far behind. Gene-editing can cure formerly incurable conditions such as sickle cell disease. It is also a powerful research tool for understanding the biology and mechanisms of disease and developing new treatments and therapeutics. This will be increasingly true as AI is deployed to understand the vast amounts of genomic and health data now available.

Two major sources of inequity remain and threaten to get worse if all consideration of diversity, equity, and inclusion are removed from NIH-funded studies. One is that we do not understand the impact on health of many of the genetic variants found in more variable genomes; this inequity will only increase if biased data sets are used to train AI models. This will mean a decrease in our ability to diagnose genetic conditions and to discover treatments and cures that will work for everyone. The other is a continued inequity in access to genomic diagnostics and treatments, which are often not covered by insurance and are not even available in all areas. Therefore, there is still a danger that genomics as a tool will increase, rather than decrease, health inequities. I don’t know how we prevent this without a focus on diversity, equity, and inclusion in all genomic biomedical research efforts and resulting public health initiatives. We must work together to close the equity gap, not increase it!

* Should the site ever be removed or altered, you can find the current version here, thanks to the those at The Internet Archive: https://web.archive.org/web/20260331150239/https://www.genome.gov/about-genomics/History-of-Genomics-Program