“People may assume that they are being provided accurate medical grade testing, so understandably do not go to the trouble and expense of seeking confirmation.”
Genetic information is extremely valuable and informative, but it’s equally complicated and difficult to interpret. As direct-to-consumer (DTC) genetic testing continues to boom, more patients have access to that data than ever—but most primary care doctors don’t have the expertise to parse meaning from genetic results, and there’s a dearth of trained experts who do.
That’s important, because as many as 40% of DTC tests may contain false positives.
In a report published this week in Genetics in Medicine, a Nature journal, researchers at a clinical laboratory re-tested 49 patients’ samples and compared them to raw data from their DTC tests. Two in 5 variants in the DTC information were incorrectly reported.
“Such a high rate of a false positives in this particular study was unexpected,” lead researcher Stephany Leigh Tandy-Connor said. Of all the BRCA1 and 2 variants in the study, for example, 17 were correctly identified, while 8 were false positives. Across the study, 94% of the false-positive calls were for cancer-related genes.
This could be due to how those companies conduct their testing. According to the report, many DTC labs use a single-nucleotide polymorphism genotyping array: The authors say that gives them an incomplete view of a person’s genetics.
“This is not comprehensive full-gene sequencing, nor does it include gross deletion or duplication analyses, which are both routinely part of clinical diagnostic testing,” the authors wrote. “Even when comparing single-nucleotide polymorphism arrays between DTC companies, it is possible to see a high degree of variability, as probe coverage varies between companies.”
Ambry Genetics in Aliso Viejo, California ran the study. They used either Sanger or next-generation sequencing when verifying the results.
The team also made another surprising finding. With the exception of a 10-condition test that 23andMe was recently approved to sell, most DTC testing companies are barred from selling their tests as diagnostics. But most will release the raw data to a patient upon request, and the report identified a growing industry of third-party companies who will perform diagnostic analysis of this data—often badly.
The report details the case of a patient whose physician was attempting to rule out Ehlers-Danlos syndrome. Some COL3A1 mutations are associated with the disease, and the patient presented their clinician with third-party interpretation of raw data from a DTC test showing presence of 1 such mutation and 4 COL5A1 mutations.
Ambry Genetics could not detect the COL3A1 variant, and even if it had, the specific mutation shown in the third-party DTC interpretation was considered benign (as are 3 of the 4 COL5A1 mutations). All of the variants had been incorrectly marked as increasing that patient’s risk of the disease.
The raw data include disclaimers stating that they aren’t intended for medical use, but that doesn’t mean they couldn’t have “significant implications” for patient behavior and care if misinterpreted. The associated costs from unnecessary procedures or additional testing have yet to be seen.
“While DTC results may lead to healthy changes in lifestyle or diet, these could also result in unwarranted emotions, including anxiety when someone obtains unexpected information, inaccurate information, or disappointment when receiving a lack of comprehensive diagnostic analysis,” Tandy-Connor said.
The size of the study—only 49 patients—might itself evidence the scale of the problem. While DTC testing is extremely popular, the samples tested in the study all came from Ambry’s internal databases: They represent people who shared their test results with their medical providers, who in turn decided that the findings warranted clinical interpretation. Given the newness of the field, those precautionary actions on behalf of both doctor and patient may still be rare.
“People may assume that they are being provided accurate medical grade testing, so understandably do not go to the trouble and expense of seeking confirmation,” according to Tandy-Connor.