Published on February 25, 2021
Study Reveals At-Home Genetic Testing Can Falsely Detect Rare Mutations
A genetic testing technology that is commonly used by DNA and ancestry companies, such as 23andMe, is “extremely unreliable” in detecting very rare mutations, including those that can predict breast cancer, according to a recent study published in the BMJ.
The large-scale study was conducted by a team at the University of Exeter in the United Kingdom, after hearing of cases where women had wrongly been told they had very rare genetic variations in the BRCA1 gene, increasing their risk of breast cancer.
The women scheduled “invasive medical procedures that were both unnecessary and unwarranted,” said Dr. Caroline Wright, a professor in genomic medicine at the University of Exeter Medical School and the study’s senior author, in a press release. The test, called SNP for single nucleotide polymorphism, is widely used by commercial companies that offer genetic testing to consumers.
While SNP tests are “excellent” at detecting genetic variations that can increase the risk of diseases, such as type 2 diabetes, they are “extremely poor at detecting very rare disease-causing genetic variants, often giving false-positive results that can have profound clinical impact,” Dr. Wright said.
What Exactly Did the Study Find?
Researchers compared data from SNP chips with data from next-generation sequencing, a DNA test with high accuracy for rare genetic variants, in nearly 50,000 participants of the UK Biobank and an additional 21 people who shared consumer genetic test results via the Personal Genome Project. The biobank is a research repository of in-depth genetic and health information from 500,000 people who live in the UK.
For very rare variants (occurring in fewer than 1 in 100,000) that cause individuals to be predisposed to rare genetic diseases, 84% of results in the UK Biobank data were false positives. In the data from the consumers, 20 of the 21 individuals had at least one false-positive rare disease-causing variant that had been incorrectly genotyped.
"The number of false positives on rare genetic variants produced by SNP chips was shockingly high,” said Dr. Leigh Jackson, a lecturer in genomic medicine at the University of Exeter and co-author of the paper, in the release. “To be clear: a very rare, disease-causing variant detected using an SNP chip is more likely to be wrong than right.”
So, Should I Ignore the Health Data from Home DNA Testing?
No, according to Dr. Wright. She told CNN she believes credible genetic testing companies can and should validate the results before releasing the information to consumers.
Indeed, an Ancestry spokesperson told CNN that AncestryHealth confirmed rare disease findings via a lab certified by the Center for Medicare and Medicaid Services as part of the Clinical Laboratory Improvement Amendments (CLIA) regulations. (While AncestryHealth was discontinued last month, Ancestry still supports the existing customers.)
"It is true that SNP chips do not detect very rare, single-point mutations, as well as sequencing, can—this has been a well-known and validated fact for many years," Gina Spatafore told the network. "That's why health results provided through our AncestryHealth product are fully validated in CLIA laboratories before they are reported to our customers.”
Dr. Wright acknowledged that some companies perform sequencing to validate the results before releasing them. However, most consumers also download their "raw" SNP chip data, which still contains the incorrect results. She said people sometimes also upload their raw data to third-party websites for further analysis.
“The implications of our findings are very simple,” Dr. Wright said. “SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient's medical care unless they have been validated."
What Does This Mean for Me?
If you take a DIY genetic test, make sure you know the limitations.
A positive result for a certain variant doesn’t necessarily mean you are at an increased risk; a negative result doesn’t necessarily mean you’re not at risk since there could be other mutations that the test didn’t detect. For example, most home genetic tests only test for the three most well-known and researched types of breast cancer.
“In addition, people with symptoms or a family history of breast and/or ovarian cancer who have received a negative SNP chip result should not be reassured that their risk is low…,” the study authors wrote. “We, therefore, urge clinicians to validate any SNP chip results from direct-to-consumer companies or research biobanks by using a standard diagnostic test before recommending any clinical action.”
The CDC echoes that recommendation, pointing out that an at-home genetic test may not give you a full understanding of your breast cancer risk. Aside from non-BRCA gene mutations, the tests do not consider non-genetic factors, such as family history.
“If you think you may be at higher risk for breast cancer,” the agency advises, “it is best to work with a doctor or genetic counselor who can assess your risk, interpret your results and build an action plan.”
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