At-Home Genetic Tests’ “Shotgun Approaches” Lead to False Positives
The results from Julie Kennerly-Shah’s at-home genetic test were alarming.
“It was very scary,” says Kennerly-Shah, a doctor of pharmacy and an assistant director in the Department of Pharmacy at The Ohio State University Wexner Medical Center.
Kennerly-Shah and her husband, radiologist Summit Shah, were on a medical mission trip to Malawi in Africa when they first received the frightening report, which was compiled via a website called Promethease using information obtained from a direct-to-consumer (DTC) genetic test purchased from the company 23andMe.
“His results were unremarkable, but mine indicated that I had two highly actionable results—for Lynch syndrome (an inherited genetic mutation that causes colon and endometrial cancers) and for hypertrophic cardiomyopathy (a disease in which the heart muscle becomes abnormally thick and can lead to sudden heart attacks).”
But here’s the thing: Kennerly-Shah’s results were false-positives, which means she doesn’t have either of those mutations. And while that revelation provided relief, the process of learning that truth was nerve-wracking and expensive, playing out over a period of weeks and requiring a consultation with a genetic counselor that added $100 in out-of-pocket costs to the $475 she paid for the 23andMe test.
False-positive results like those experienced by Kennerly-Shah are actually quite common among DTC genetic test users.
“A recent study found that about 40 percent of the results that tell people they have a genetic disorder are false-positives,” says Heather Hampel, MS, LGC, the associate director of the Division of Human Genetics of The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James), where Kennerly-Shah underwent the follow-up testing that revealed her DTC test’s errors.
While Hampel acknowledges that DTC genetic tests can provide some fun and interesting information about a person’s ethnic background, buyers should beware when using the tests in efforts to identify possible genetic mutations.
“The DTC genetic tests are great for finding out about your ancestry and your countries of origin—they’re accurate with that,” Hampel says. “There have been cases where it’s helped people contact relatives they’ve never met.”
Limitations Lead to False Positives—And Possibly Worse
Problems with the DTC tests arise, according to Hampel, when consumers’ curiosity about their family histories leads to questions about the presence of possible genetic disorders, answers to which require more sophisticated methods than those provided by at-home kits like those available for purchase through 23andMe, as well as Ancestry.com, FamilyTreeDNA and others.
“They take what I call a shotgun approach,” Hampel says. “They take a bunch of snippets of your genome, and the depth of coverage isn’t very deep. This is why they can make mistakes.”
While false-positives like those delivered to Kennerly-Shah can cause serious anxiety, it’s the possibility of the opposite that is of particular concern to Hampel.
“There hasn’t been any research on this yet, but down the road we could see incidences of people who were given negative results from these DTC genetic tests who do in fact have a genetic mutation,” she says. “This is why it’s so important to talk to your primary care physician about your family history and see a genetic counselor if warranted, and get a medical-grade genetic test.”
On the Promethease website, customers are advised that the results they receive are “for educational and research purposes only.” The company advises users to “confirm any significant finding discovered in part through the use of Promethease by an independent, clinically-validated test for use in connection with the medical trait in question.”
In spite of the format’s limitations, a recent FDA authorization granted to 23andMe to report on three specific BRCA1 and BRCA2 genetic mutations has led Hampel to believe that the test is likely accurate in the identification of those variations, which increase the risk of breast cancer and ovarian cancer in women and prostate cancer in men—though she maintains that consumers should remain cautious.
“They’re only testing for three mutations—the mutations that are most common in Jewish individuals with an Eastern European lineage,” she says. “A non-Jewish person is very unlikely to have one of these three mutations, and getting a negative result could mistakenly cause a woman to think she didn’t have any of the approximately 1,500 other BRCA mutations.”
Though there are some DTC companies that offer medical-grade genetic testing for conditions such as cancer and high cholesterol, Hampel believes the highly-complicated work of interpreting and understanding the results should become part of regular, in-person interactions between patients and their healthcare providers.
“There is the potential, in the not-so-distant future, for genetic testing to be part of the standard of care for healthy people and part of a standard physical exam. We’ll be able to find a lot of people with actionable genetic mutations,” she says. “For example, there are more than a million people walking around today with a Lynch syndrome gene mutation, and more than a million with a BRCA mutation, who don’t know it. We can prevent a lot of cancer, or catch it in the early stages when it’s very treatable and save a lot of lives.”
The false-positive results provided to Kennerly-Shah didn’t endanger her life, but they did lead to weeks of unnecessary stress and fear. Still, she believes the potential knowledge provided by the DTC tests is worth the risk—as long as users begin the process with their eyes open.
“I would do it all over again. I like information and knowing. But you have to go into it with the right mindset, that there is a good chance of a false-positive… and that when you get a positive for a genetic disorder, you need to see an expert like Heather.”
To make an appointment with a genetic counselor at the OSUCCC – James, please call 800-293-5066.