by Emily Wiljer
Graphic design by Anaiah Reyes
Who gets to be included in genetics research? Who is willing to have their genome be read like a book? When you read an article claiming the APOE4 gene is linked to Alzheimer’s, what population does that apply to? As of June 2021, 86.3% of all published genetics association studies have been done on White European populations.1 But why is this the case? Is it a research protocol? Or does this stem from a long history of distrust and misuse of data? In reality, it is a complicated blend of both that can be exemplified by the ways genomics has failed Indigenous communities across the globe.
Genomics is the study of how genes interact with each other and the environment to predict phenotypic variation and disease.2 This approach has been imperative for the development of precision medicine. However, it does not affect all populations equally: there is an underlying flaw in genomics when it comes to equality and representation. Many genetic association studies must be done with a common “genetic ancestry” in participants to limit differences in genetic variability that occur across different populations due to gene flow and global dispersion (the movement of genetic variants across populations and geographic locations).3 However, population substructure is often stratified by self-reported race as a proxy for genetic ancestry. This creates a divide amongst subgroups and fails to account for mixed raced (termed admixture) levels of population that are more representative of society.3 Because of this assumption, research will often focus on groups of “White” European ancestry, as this population constitutes the largest available data pool.
It is clear that research protocols themselves call for racial stratification, but the question persists of how we can expand the data availability to include a more diverse and representative population. Indigenous data in genetic research is vastly underrepresented, included in only 0.02% of genetic association studies published globally in 2019.4 Consequently, there is a lack of reference for genetic variants in Indigenous populations, which is needed to draw clinically relevant conclusions. Although researchers are starting to acknowledge a need for an expansion in data, the barrier goes both ways. Harm and misuse of Indigenous biological samples in research is rampant globally and throughout history. A lack of applicable results, informed consent, community involvement, and a perpetuation of stereotypes has created a pattern of distrust and has made Indigenous communities less compelled to participate in genetic research.4
One of the most famous examples concerns the Havasupai Tribe in Arizona, USA. In 1989, Arizona State Researcher, Therese Markow, was recruited to perform a genetic study with the promise of community engagement and education on the prevalence of diabetes. What the study participants didn’t know was that the researchers, without approval, went on to use the samples given by the tribe in studies on schizophrenia, migration, alcoholism, and inbreeding. When these studies came out, a lawsuit was filed by the Havasupai Tribe for misuse and lack of informed consent. They felt that such studies, on topics taboo to their community, performed harm both culturally and dignitary to the group.4,5 This clear undermining of informed consent created a decades long legal battle for the Havasupai and a foundation of distrust and skepticism when consenting to research.
In British Columbia, Canada, the Nuu-chah-nulth people had a similar experience. Dr. Ryk Ward from the University of British Columbia (UBC) was recruited to test DNA samples to potentially identify why rheumatoid arthritis was so frequent and severe in this community. Dr. Ward never completed the study on rheumatoid arthritis, but brought the samples with him when he moved around the world for academic appointments. In total, over 100 papers were published that included the Nuu-chah-nulth people’s DNA, including studies on human migration and retroviruses⁴. However, it was not until the release of a documentary inspired by Dr. Ward’s genetic studies that the Nuu-chah-nulth were aware of this secondary use of their samples. The community worked with UBC to recover their samples and formed their own research ethics committee to ensure that their consent would not be violated again in such a manner.4
Beyond lack of consent, an egregious ethics violation in itself, Indigenous DNA data has also been used to propagate negative and harmful stereotypes of their communities. In New Zealand, the Māori community was part of a study concerned with high and low-nicotine metabolism. The researchers made claims of a “warrior gene” that linked Polynesian migration routes, aggressive behavior in monkeys, and Māori smoking cessation rates, despite the fact that the genetic variation being studied was present in all populations globally⁴. This blatant and inaccurate insult led to a publicly understood reluctance from the Māori community to participate in further genetics research, and increased their distrust in the scientific community.4
These stories are not isolated incidents. As we enter the age of precision medicine and genomics, we must strive to learn from these events. To scientists, biological samples may be a means to an end, but to some cultures, including some Indigenous populations, they mean much more. Dr. Frank Dukepoo, a Hopi geneticist, described this relationship: “To us, any part of ourselves is sacred. Scientists say it’s just DNA. For an Indian, it is not just DNA, it is part of a person, it is sacred, with deep religious significance. It is part of the essence of a person.”6
Going forward, we must analyze how we approach genomics, not only by questioning our own practices but by considering why some people may be more reluctant to share their DNA, especially minority populations who have been targeted historically. Recognition of sovereignty, community-engaged research, and effective guidelines built in partnership with Indigenous, or other minority communities should lay a clear and constructive path forward for diversity in genomics.4
References
1. Fatumo S, Chikowore T, Choudhury A, Ayub M, Martin AR, Kuchenbaecker K. A roadmap to increase diversity in genomic studies. Nat Med. 2022;28(2):243-250. doi: 10.1038/s41591-021-01672-4.
2. Gwynne K, Jiang S, Venema R, Christie V, Boughtwood T, Ritha M, et al. Genomics and inclusion of indigenous peoples in high income countries. Hum Genet. 2023 Sep;142(9):1407-1416. doi: 10.1007/s00439-023-02587-5.
3. Race, Ethnicity, and Genetics Working Group. The use of racial, ethnic, and ancestral categories in human genetics research. Am J Hum Genet. 2005 Oct;77(4):519-32. doi: 10.1086/491747.
4. Garrison NA, Hudson M, Ballantyne LL, Garba I, Martinez A, Taualii M, et al. Genomic research through an indigenous lens: Understanding the expectations. Annual Reviews; 2019(20):495-517. https://doi.org/10.1146/annurev-genom-083118-015434
5. Sterling RL. Genetic research among the havasupai: A cautionary tale. Virtual Mentor. 2011;13(2):113-117. doi: 10.1001/virtualmentor.2011.13.2.hlaw1-1102
6. Petit C. Trying to study tribes while respecting their cultures / hopi Indian geneticist can see both sides . 1998. Available from: https://www.sfgate.com/news/article/Trying-to-Study-Tribes-While-Respecting-Their-3012825.php
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