Boston ABE teacher Amanda Dillingham and colleagues had some tough questions about genetics and ethnicity that arise in their biology classes, so they turned to an expert, Amgen senior scientist Luke Ward. In Part 2 of this two-part series, Ward talks about the differences between race and ethnicity when working in genetics and personalized medicine. Read Part 1.
Dillingham and team: How do race, ethnicity, and population play into genetics studies for medicine? What thoughts do you have on how teachers can differentiate the socio-political construct of race and the biological underpinnings of ethnicity in the biology classroom?
Ward: Race is a socially-constructed category. There can be large disconnects between how people personally identify and construct community, how people are impacted daily by prejudice and racism, and what a genetic test might reveal about someone’s ancestry.
The terms “ethnicity,” “population,” and “ancestry” get closer to the idea of biologically relevant genetic relationships and similarities, and so you will hear biologists use those terms more often than “race.” However even these terms can be ambiguous and tricky. For example, when we say ancestry, are we talking about where your ancestors lived centuries ago before mass migration? Or hundreds of millennia ago, when they were all in Africa? Are we talking about how those ancestors would have identified in terms of nationality or religion, or are we talking about their skin color? Or are we talking about identities in our country today that can serve as a proxy for socioeconomic factors?
It’s important to understand the nature of genetic variation across our species, and that it does not correspond to the discrete categories that we think of as races. It’s also important to look to the social sciences to understand how race has been constructed differently in various historical settings and how systematic racism affects health.
Direct-to-consumer ancestry tests can indeed accurately assign chunks of your genome to the places in the world that they once inhabited centuries ago. But these algorithms are using subtle patterns of allele frequencies to make these guesses, and the results are only as accurate as the reference populations they are using for comparison. The limited resolution of these ancestry assignments can produce an illusion of categorical “races” and the misconception of more fundamental differences than there really are.
Kay Young McChesney has written an excellent review of the science of these topics for teachers, and Joseph L. Graves Jr. has provided an outstanding essay for the Southern Poverty Law Center’s Teaching Tolerance magazine. Yudell et al. have recently published an essay on this topic for a scientific audience.
Dillingham and team: Can you talk a bit more about how ancestry and ethnicity relate to personalized medicine?
Ward: There are a few ways in which genetic ancestry complicates how we might think about individualized therapies and precision medicine.
The first issue is that, although all humans have the same set of about 20,000 genes and those genes have the same essential function in all people, the ways in which those genes are “broken” in rare genetic diseases can be different based on the ancestral population in which the mutation arose. So if a therapeutic for a rare genetic disease works through targeting the mutation, it may only work in one subset of all the patients with disorders related to that gene, and thus would have a disparate impact based on genetic ancestry.
The other issue is that most human genetics research has been done in European populations, and that bias can affect our understanding of genetic disease. Specifically, the field of medical and clinical genetics, which often must tackle the interpretation of rare mutations seen in patients, can make more accurate diagnoses when a mutation has been studied previously. At worst, this bias can lead to misdiagnosis.
The most important direction in genetics is not ethnicity-based studies per se, but ethnically diverse studies that capture gene-phenotype relationships using the widest possible sampling of genetic variation and environments.
Dillingham and team: What trends do you see in the scientific and medical communities of linking race and medicine? Is modern genetics allowing us to move past this into more ethnicity-based studies? By giving doctors genetic data, will it help with implicit bias?
Ward: The scientific community I’m most familiar with, the group of scientists who study human population genetics, has been active in rebutting claims that the minor genetic differences between ancestral groups are useful for explaining the major health disparities that are actually driven by structural inequality. However, diversifying genetic studies is critical. In my opinion the most important direction in genetics is not ethnicity-based studies per se but ethnically diverse studies that capture gene-phenotype relationships using the widest possible sampling of genetic variation and environments.
Unfortunately race is still used as an imperfect proxy for when doing medical diagnosis, as medical student Jennifer Tsai explained in a recent essay. When doctors use race as a proxy for genetics, it can further exacerbate health disparities. One example is cystic fibrosis, caused by mutations that are most prevalent in people with European ancestry; the assumption that it cannot occur in other populations has led to delayed diagnosis of cystic fibrosis in children who doctors identify as non-white. If these children had been sequenced at birth, a cystic fibrosis diagnosis could have been suspected immediately.
Reading and References:
- Hamburg, M.A. and F.S. Collins, The path to personalized medicine. N Engl J Med, 2010. 363(4): p. 301-4.
- Brenner, M.K., Personalized medicine: words that mean just what you choose? Mol Ther, 201 20(2): p. 241-2.
- Collins, F.S. and H. Varmus, A new initiative on precision medicine. N Engl J Med, 2015. 372(9): p. 793-5.
- Murray, J.F., Personalized medicine: been there, done that, always needs work! Am J Respir Crit Care Med, 2012. 185(12): p. 1251-2.
- Senn, S., Statistical pitfalls of personalized medicine. Nature, 2018. 563(7733): p. 619-621.
- Kim, S., et al., Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines. Ann Lab Med, 2017. 37(2): p. 180-193.
- Drozda, K., et al., Pharmacogenetic Labeling of FDA-Approved Drugs: A Regulatory Retrospective. JACC Basic Transl Sci, 2018. 3(4): p. 545-549.
- Ma, J.D., K.C. Lee, and G.M. Kuo, Clinical application of pharmacogenomics. J Pharm Pract, 2012. 25(4): p. 417-27.
- McChesney, K.Y., Teaching diversity: The science you need to know to explain why race is not biological. SAGE Open, 2015. 5(4): p. 2158244015611712.
- Joseph L. Graves, J. Race ≠ DNA: If race is a social construct, what’s up with DNA ancestry testing? Teaching Tolerance.
- Yudell, M., et al., SCIENCE AND SOCIETY. Taking race out of human genetics. Science, 2016. 351(6273): p. 564-5.
- Popejoy, A.B. and S.M. Fullerton, Genomics is failing on diversity. Nature, 2016. 538(7624): p. 161-164.
- Manrai, A.K., et al., Genetic misdiagnoses and the potential for health disparities. N Engl J Med, 2016. 375(7): p. 655-65.
- Kaye, J.B., et al., Warfarin pharmacogenomics in diverse populations. Pharmacotherapy, 2017. 37(9): p. 1150-1163.
- Letters: ‘A Troublesome Inheritance’, in The New York Times. 2014.
- Tsai, J.W., You can’t tell a book by its cover — or a disease by Drake’s race, in STAT News.
- Stewart, C. and M.S. Pepper, Cystic Fibrosis in the African Diaspora. Ann Am Thorac Soc, 20 14(1): p. 1-7.