Low numbers of minorities in medical genetic studies is bad for both science and society.
By Michael White
(Photo: Leon Neal/AFP/Getty Images)
The next big thing in medicine is supposed to be precision medicine — medical care that is more effective because it is individually tailored to each person, largely on the basis of genetics. Precision medicine has long been an important goal of physicians and biomedical scientists, and it is now the focus of a major new research initiative introduced by the Obama administration. But if we’re going to realize this dream fairly, then we have a big problem: Our genetic studies are leaving out ethnic and racial minorities. Those minorities, whose medical care has long lagged behind that of white Americans, are at risk of being left out of what is supposed to be a major new development in medicine.
Shortly after the first of a new generation of genome-based health studies began to appear, a 2009 report warned that the racial make-up of these studies — conducted largely in the United States and the United Kingdom — was badly skewed. There were 10 times more studies of individuals of European ancestry than there were of all other groups combined, including Asians, Hispanics, and Africans or African Americans. The authors warned that, “to avoid the genetics community contributing to healthcare disparities, it is important to adopt measures to ensure that populations of diverse ancestry are included in genomic studies.”
A new report published this month suggests that things haven’t improved much since then. Whites of European ancestry still make up the vast majority of subjects in large genetic studies — over 80 percent. There has been an increase in genetic studies of Asians, who have gone from representing 3 percent of genetic study populations in 2009 to 14 percent today. This reflects the increased investment in genetics research by Asian countries, especially China.
But Africans, African Americans, and Hispanics still make up less than 4 percent of the subjects of these studies. The report’s authors, Alice Popejoy and Stephanie Fullerton at the University of Washington, write that, given the enormous increase in the number of genetic studies conducted since 2009, “the lack of growth in representation from other populations is remarkable and deeply disconcerting.”
We should be disconcerted, though these numbers do come with a few caveats. As Popejoy and Fullerton note, many genetic studies reuse and reanalyze data from earlier studies, meaning that some European ancestry-biased study populations are counted multiple times in their analysis. Newer cohorts with a more racially diverse make-up haven’t yet been reused as often.
Furthermore, there were good scientific reasons why early genomic studies focused on people of European ancestry. Assembling and evaluating thousands of people for a medical study requires a lot of infrastructure, and so early genomic studies piggy-backed onto existing study cohorts — like the famed Framingham Heart Study, which has been running since 1950 and currently includes over 10,000 people. This was an efficient way to get genomic studies off the ground, but it also means that those studies reflect the lamentable lack of diversity in established cohorts of human subjects.
A more important justification for the lack of racial diversity has to do with the limits of the DNA technology and analysis methods that were state-of-the-art in 2009. To have a decent chance of detecting a relationship between a genetic mutation and disease, researchers needed to minimize other genetic variables that might confound the results. Genetic differences in ancestry can mask a relationship between mutations and disease. That means the mixed ancestry of Hispanics and African Americans made them more difficult to study than more genetically homogeneous whites of European ancestry.
These scientific justifications for avoiding diversity, however, no longer hold. Today, we have well-established, robust statistical methods for handling mixed ancestry populations, and more comprehensive DNA analysis technologies that make it easier to collect useful data from a more diverse set of human subjects. In fact, the demands of good science are now pointing the other way — a lack of diversity in genetic studies is no longer helping, but rather hindering the scientific progress of medical genetics and precision medicine.
To see why, it’s important to first understand that different genetic mutations, whether connected to a disease or not, are often common in one population but rare in another. A mutation that increases the risk for breast cancer, for example, might be much more frequent among African Americans than among whites of European descent. Such mutations might not be detected at all in studies that include mainly whites, with the result that researchers miss an important genetic cause of breast cancer. The problem runs the other way as well: A mutation that is rare among whites might be mistakenly linked with a disease, but actually turn out to be benign and relatively common in other populations. By failing to properly capture the full range of human genetic diversity, researchers will be left with an incomplete and misleading understanding of the genetic basis of disease.
This incomplete understanding means that genetic tests, one of the basic tools of precision medicine, often don’t perform very well on Hispanics or African Americans. A study published earlier this year found that the poor representation of minority populations in genetic studies makes it difficult to sift out the signal from the noise in genetic testing of non-whites. An August study in The New England Journal of Medicine found that genetic tests for one type of heart disease frequently misclassified African Americans as having a high genetic risk, when, in fact, they didn’t. The researchers observed that “the inclusion of even small numbers of black Americans in control cohorts [of genetic studies] probably would have prevented these misclassifications.”
How do we solve the diversity problem in genetics? Fortunately, major efforts to include African Americans and Hispanics in large genetic studies are now coming to fruition. The National Institutes of Health is supporting several long-term, resource-intensive study cohorts that better represent minority populations, such as the Multi-Ethnic Study of Atherosclerosis and the Hispanic Community Health Study. And because many genetic studies rely on data from already existing study populations, it is also critical to encourage researchers to share and reuse data from newer cohorts that include more minority populations. The National Cancer Institute just launched an effort to do this for breast cancer genetics in African-American women.
Ultimately, solving the diversity problem in genetics is not just the NIH’s responsibility — it belongs to the community of researchers more broadly, who, as teams and individuals, decide how to design their genetic studies. If researchers fail to improve diversity in genetics, they will worsen existing health disparities between whites and non-whites — and that’s inexcusable for a community that claims to be creating the medicine of the future.