Genetic Testing Companies Are Facing a Racial Bias Problem in Disease Risk Tests
The large genetic studies underlying certain disease risk tests have primarily been done in populations of European ancestry, limiting their accuracy.
Earlier this year, California-based Ambry Genetics announced that it was discontinuing a test meant to estimate a person's risk of developing prostate or breast cancer. The test looks for variations in a person's DNA that are known to be associated with these cancers.
Known as a polygenic risk score, this type of test adds up the effects of variants in many genes — often in the dozens or hundreds — and calculates a person's risk of developing a particular health condition compared to other people. In this way, polygenic risk scores are different from traditional genetic tests that look for mutations in single genes, such as BRCA1 and BRCA2, which raise the risk of breast cancer.
Traditional genetic tests look for mutations that are relatively rare in the general population but have a large impact on a person's disease risk, like BRCA1 and BRCA2. By contrast, polygenic risk scores scan for more common genetic variants that, on their own, have a small effect on risk. Added together, however, they can raise a person's risk for developing disease.
These scores could become a part of routine healthcare in the next few years. Researchers are developing polygenic risk scores for cancer, heart, disease, diabetes and even depression. Before they can be rolled out widely, they'll have to overcome a key limitation: racial bias.
"The issue with these polygenic risk scores is that the scientific studies which they're based on have primarily been done in individuals of European ancestry," says Sara Riordan, president of the National Society of Genetics Counselors. These scores are calculated by comparing the genetic data of people with and without a particular disease. To make these scores accurate, researchers need genetic data from tens or hundreds of thousands of people.
Myriad's old test would have shown that a Black woman had twice as high of a risk for breast cancer compared to the average woman even if she was at low or average risk.
A 2018 analysis found that 78% of participants included in such large genetic studies, known as genome-wide association studies, were of European descent. That's a problem, because certain disease-associated genetic variants don't appear equally across different racial and ethnic groups. For example, a particular variant in the TTR gene, known as V1221, occurs more frequently in people of African descent. In recent years, the variant has been found in 3 to 4 percent of individuals of African ancestry in the United States. Mutations in this gene can cause protein to build up in the heart, leading to a higher risk of heart failure. A polygenic risk score for heart disease based on genetic data from mostly white people likely wouldn't give accurate risk information to African Americans.
Accuracy in genetic testing matters because such polygenic risk scores could help patients and their doctors make better decisions about their healthcare.
For instance, if a polygenic risk score determines that a woman is at higher-than-average risk of breast cancer, her doctor might recommend more frequent mammograms — X-rays that take a picture of the breast. Or, if a risk score reveals that a patient is more predisposed to heart attack, a doctor might prescribe preventive statins, a type of cholesterol-lowering drug.
"Let's be clear, these are not diagnostic tools," says Alicia Martin, a population and statistical geneticist at the Broad Institute of MIT and Harvard. "We can't use a polygenic score to say you will or will not get breast cancer or have a heart attack."
But combining a patient's polygenic risk score with other factors that affect disease risk — like age, weight, medication use or smoking status — may provide a better sense of how likely they are to develop a specific health condition than considering any one risk factor one its own. The accuracy of polygenic risk scores becomes even more important when considering that these scores may be used to guide medication prescription or help patients make decisions about preventive surgery, such as a mastectomy.
In a study published in September, researchers used results from large genetics studies of people with European ancestry and data from the UK Biobank to calculate polygenic risk scores for breast and prostate cancer for people with African, East Asian, European and South Asian ancestry. They found that they could identify individuals at higher risk of breast and prostate cancer when they scaled the risk scores within each group, but the authors say this is only a temporary solution. Recruiting more diverse participants for genetics studies will lead to better cancer detection and prevent, they conclude.
Recent efforts to do just that are expected to make these scores more accurate in the future. Until then, some genetics companies are struggling to overcome the European bias in their tests.
Acknowledging the limitations of its polygenic risk score, Ambry Genetics said in April that it would stop offering the test until it could be recalibrated. The company launched the test, known as AmbryScore, in 2018.
"After careful consideration, we have decided to discontinue AmbryScore to help reduce disparities in access to genetic testing and to stay aligned with current guidelines," the company said in an email to customers. "Due to limited data across ethnic populations, most polygenic risk scores, including AmbryScore, have not been validated for use in patients of diverse backgrounds." (The company did not make a spokesperson available for an interview for this story.)
In September 2020, the National Comprehensive Cancer Network updated its guidelines to advise against the use of polygenic risk scores in routine patient care because of "significant limitations in interpretation." The nonprofit, which represents 31 major cancer cancers across the United States, said such scores could continue to be used experimentally in clinical trials, however.
Holly Pederson, director of Medical Breast Services at the Cleveland Clinic, says the realization that polygenic risk scores may not be accurate for all races and ethnicities is relatively recent. Pederson worked with Salt Lake City-based Myriad Genetics, a leading provider of genetic tests, to improve the accuracy of its polygenic risk score for breast cancer.
The company announced in August that it had recalibrated the test, called RiskScore, for women of all ancestries. Previously, Myriad did not offer its polygenic risk score to women who self-reported any ancestry other than sole European or Ashkenazi ancestry.
"Black women, while they have a similar rate of breast cancer to white women, if not lower, had twice as high of a polygenic risk score because the development and validation of the model was done in white populations," Pederson said of the old test. In other words, Myriad's old test would have shown that a Black woman had twice as high of a risk for breast cancer compared to the average woman even if she was at low or average risk.
To develop and validate the new score, Pederson and other researchers assessed data from more than 275,000 women, including more than 31,000 African American women and nearly 50,000 women of East Asian descent. They looked at 56 different genetic variants associated with ancestry and 93 associated with breast cancer. Interestingly, they found that at least 95% of the breast cancer variants were similar amongst the different ancestries.
The company says the resulting test is now more accurate for all women across the board, but Pederson cautions that it's still slightly less accurate for Black women.
"It's not only the lack of data from Black women that leads to inaccuracies and a lack of validation in these types of risk models, it's also the pure genomic diversity of Africa," she says, noting that Africa is the most genetically diverse continent on the planet. "We just need more data, not only in American Black women but in African women to really further characterize that continent."
Martin says it's problematic that such scores are most accurate for white people because they could further exacerbate health disparities in traditionally underserved groups, such as Black Americans. "If we were to set up really representative massive genetic studies, we would do a much better job at predicting genetic risk for everybody," she says.
Earlier this year, the National Institutes of Health awarded $38 million to researchers to improve the accuracy of polygenic risk scores in diverse populations. Researchers will create new genome datasets and pool information from existing ones in an effort to diversify the data that polygenic scores rely on. They plan to make these datasets available to other scientists to use.
"By having adequate representation, we can ensure that the results of a genetic test are widely applicable," Riordan says.
Chicken that is grown entirely in a laboratory, without harming a single bird, could be sold in supermarkets in the coming months. But critics say the doubts about lab-grown meat have not been appropriately explored.
Last November, when the U.S. Food and Drug Administration disclosed that chicken from a California firm called UPSIDE Foods did not raise safety concerns, it drily upended how humans have obtained animal protein for thousands of generations.
“The FDA is ready to work with additional firms developing cultured animal cell food and production processes to ensure their food is safe and lawful,” the agency said in a statement at the time.
Assuming UPSIDE obtains clearances from the U.S. Department of Agriculture, its chicken – grown entirely in a laboratory without harming a single bird – could be sold in supermarkets in the coming months.
“Ultimately, we want our products to be available everywhere meat is sold, including retail and food service channels,” a company spokesperson said. The upscale French restaurant Atelier Crenn in San Francisco will have UPSIDE chicken on its menu once it is approved, she added.
Known as lab-grown or cultured meat, a product such as UPSIDE’s is created using stem cells and other tissue obtained from a chicken, cow or other livestock. Those cells are then multiplied in a nutrient-dense environment, usually in conjunction with a “scaffold” of plant-based materials or gelatin to give them a familiar form, such as a chicken breast or a ribeye steak. A Dutch company called Mosa Meat claims it can produce 80,000 hamburgers derived from a cluster of tissue the size of a sesame seed.
Critics say the doubts about lab-grown meat and the possibility it could merge “Brave New World” with “The Jungle” and “Soylent Green” have not been appropriately explored.
That’s a far cry from when it took months of work to create the first lab-grown hamburger a decade ago. That minuscule patty – which did not contain any fat and was literally plucked from a Petri dish to go into a frying pan – cost about $325,000 to produce.
Just a decade later, an Israeli company called Future Meat said it can produce lab-grown meat for about $1.70 per pound. It plans to open a production facility in the U.S. sometime in 2023 and distribute its products under the brand name “Believer.”
Costs for production have sunk so low that researchers at Carnegie Mellon University in Pittsburgh expect sometime in early 2024 to produce lab-grown Wagyu steak to showcase the viability of growing high-end cuts of beef cheaply. The Carnegie Mellon team is producing its Wagyu using a consumer 3-D printer bought secondhand on eBay and modified to print the highly marbled flesh using a method developed by the university. The device costs $200 – about the same as a pound of Wagyu in the U.S. The initiative’s modest five-figure budget was successfully crowdfunded last year.
“The big cost is going to be the cells (which are being extracted by a cow somewhere in Pennsylvania), but otherwise printing doesn’t add much to the process,” said Rosalyn Abbott, a Carnegie Mellon assistant professor of bioengineering who is co-leader on the project. “But it adds value, unlike doing this with ground meat.”
Lab-Grown Meat’s Promise
Proponents of lab-grown meat say it will cut down on traditional agriculture, which has been a leading contributor to deforestation, water shortages and contaminated waterways from animal waste, as well as climate change.
An Oxford University study from 2011 concludes lab-grown meat could have greenhouse emissions 96 percent lower compared to traditionally raised livestock. Moreover, proponents of lab-grown meat claim that the suffering of animals would decline dramatically, as they would no longer need to be warehoused and slaughtered. A recently opened 26-story high-rise in China dedicated to the raising and slaughtering of pigs illustrates the current plight of livestock in stark terms.
Scientists may even learn how to tweak lab-grown meat to make it more nutritious. Natural red meat is high in saturated fat and, if it’s eaten too often, can lead to chronic diseases. In lab versions, the saturated fat could be swapped for healthier, omega-3 fatty acids.
But critics say the doubts about lab-grown meat and the possibility it could merge “Brave New World” with “The Jungle” and “Soylent Green” have not been appropriately explored.
A Slippery Slope?
Some academics who have studied the moral and ethical issues surrounding lab-grown meat believe it will have a tough path ahead gaining acceptance by consumers. Should it actually succeed in gaining acceptance, many ethical questions must be answered.
“People might be interested” in lab-grown meat, perhaps as a curiosity, said Carlos Alvaro, an associate professor of philosophy at the New York City College of Technology, part of the City University of New York. But the allure of traditionally sourced meat has been baked – or perhaps grilled – into people’s minds for so long that they may not want to make the switch. Plant-based meat provides a recent example of the uphill battle involved in changing old food habits, with Beyond Meat’s stock prices dipping nearly 80 percent in 2022.
"There are many studies showing that people don’t really care about the environment (to that extent)," Alvaro said. "So I don’t know how you would convince people to do this because of the environment.”
“From my research, I understand that the taste (of lab-grown meat) is not quite there,” Alvaro said, noting that the amino acids, sugars and other nutrients required to grow cultivated meat do not mimic what livestock are fed. He also observed that the multiplication of cells as part of the process “really mimic cancer cells” in the way they grow, another off-putting thought for would-be consumers of the product.
Alvaro is also convinced the public will not buy into any argument that lab-grown meat is more environmentally friendly.
“If people care about the environment, they either try and consume considerably less meat and other animal products, or they go vegan or vegetarian,” he said. “But there are many studies showing that people don’t really care about the environment (to that extent). So I don’t know how you would convince people to do this because of the environment.”
Ben Bramble, a professor at Australian National University who previously held posts at Princeton and Trinity College in Ireland, takes a slightly different tack. He noted that “if lab-grown meat becomes cheaper, healthier, or tastier than regular meat, there will be a large market for it. If it becomes all of these things, it will dominate the market.”
However, Bramble has misgivings about that occurring. He believes a smooth transition from traditionally sourced meat to a lab-grown version would allow humans to elide over the decades of animal cruelty perpetrated by large-scale agriculture, without fully reckoning with and learning from this injustice.
“My fear is that if we all switch over to lab-grown meat because it has become cheaper, healthier, or tastier than regular meat, we might never come to realize what we have done, and the terrible things we are capable of,” he said. “This would be a catastrophe.”
Bramble’s writings about cultured meat also raise some serious moral conundrums. If, for example, animal meat may be cultivated without killing animals, why not create products from human protein?
Actually, that’s already happened.
It occurred in 2019, when Orkan Telhan, a professor of fine arts at the University of Pennsylvania, collaborated with two scientists to create an art exhibit at the Philadelphia Museum of Art on the future of foodstuffs.
Although the exhibit included bioengineered bread and genetically modified salmon, it was an installation called “Ouroboros Steak” that drew the most attention. That was comprised of pieces of human flesh grown in a lab from cultivated cells and expired blood products obtained from online sources.
The exhibit was presented as four tiny morsels of red meat – shaped in patterns suggesting an ouroboros, a dragon eating its own tail. They were placed in tiny individual saucers atop a larger plate and placemat with a calico pattern, suggesting an item to order in a diner. The artwork drew international headlines – as well as condemnation for Telhan’s vision.
Telhan’s artwork is intended to critique the overarching assumption that lab-grown meat will eventually replace more traditional production methods, as well as the lack of transparency surrounding many processed foodstuffs. “They think that this problem (from industrial-scale agriculture) is going be solved by this new technology,” Telhan said. “I am critical (of) that perspective.”
Unlike Bramble, Telhan is not against lab-grown meat, so long as its producers are transparent about the sourcing of materials and its cultivation. But he believes that large-scale agricultural meat production – which dates back centuries – is not going to be replaced so quickly.
“We see this again and again with different industries, like algae-based fuels. A lot of companies were excited about this, and promoted it,” Telhan said. “And years later, we know these fuels work. But to be able to displace the oil industry means building the infrastructure to scale takes billions of dollars, and nobody has the patience or money to do it.”
Alvaro concurred on this point, which he believes is already weakened because a large swath of consumers aren’t concerned about environmental degradation.
“They’re going to have to sell this big, but in order to convince people to do so, they have to convince them to eat this product instead of regular meat,” Alvaro said.
Hidden Tweaks?
Moreover, if lab-based meat does obtain a significant market share, Telhan suggested companies may do things to the product – such as to genetically modify it to become more profitable – and never notify consumers. That is a particular concern in the U.S., where regulations regarding such modifications are vastly more relaxed than in the European Union.
“I think that they have really good objectives, and they aspire to good objectives,” Telhan said. “But the system itself doesn't really allow for that much transparency.”
No matter what the future holds, sometime next year Carnegie Mellon is expected to hold a press conference announcing it has produced a cut of the world’s most expensive beef with the help of a modified piece of consumer electronics. It will likely take place at around the same time UPSIDE chicken will be available for purchase in supermarkets and restaurants, pending the USDA’s approvals.
Abbott, the Carnegie Mellon professor, suggested the future event will be both informative and celebratory.
“I think Carnegie Mellon would have someone potentially cook it for us,” she said. “Like have a really good chef in New York City do it.”
In this week's Friday Five, breathing this way may cut down on anxiety, a fasting regimen that could make you sick, this type of job makes men more virile, 3D printed hearts could save your life, and the role of metformin in preventing dementia.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.