Genetic Tests Ordered by Mail Can Give Many False Positives
If you’ve gotten a genetic test for an early riser and he tells you you have an option that puts you at risk for cancer, you should go straight to a professional for a more expensive test for confirmation. But a recent study found that an initial test done for fun gave the wrong results 40% of the time.
The study was small, only 49 people, so we don’t know if tests done directly to the consumer always give 40% of false positives; overall it could be better or it could be worse. It’s also worth noting that the people in this study were those whose results were dangerous enough to warrant seeking a professional for a clinical trial.
The study was carried out at the Ambri Genetic Laboratory, which conducts clinical trials. In a way, this makes them competitors of the tests they criticize. But companies like 23andme already point out in their disclaimer that their tests shouldn’t be your only source of medical advice, so clinical testing is often a necessary follow-up step after using these services.
How to look at your raw data
When you order a genetic test from a company like 23andme or Ancestry, the company usually doesn’t tell you everything it finds. Ancestry does not report health results at all, and 23andme only reports serious health conditions on some FDA-approved tests .
But if you’re interested, you can download a raw data file containing all the SNPs tested by the company. These are the places in your DNA where people tend to be different from each other. Some of these options are associated with a predisposition to cancer or other medical conditions. You can submit the raw data file to any of dozens of third-party analytics sites that will tell you what’s inside.
But these results – especially from third parties – are not as accurate as a clinical genetic test. If you get a result that could change your health care or prompt you to take decisive action, such as surgery, you should confirm it with a more thorough examination.
Ambry, one of the companies that conducts these more rigorous tests, reviewed their records and found that 49 people requested clinical testing because a direct-to-consumer test showed them that they had a harmful option (for example, a predisposition to cancer ). … And according to an article published in the journal Genetics in Medicine , they were able to confirm only 60 percent of those initial results.
Difference Between DTC and Clinical Tests
Direct-to-Consumer Tests (DTCs) include anything that sends saliva to a company and gets results without even talking to a doctor or other healthcare professional. Clinical testing, on the other hand, is prescribed by a physician, and testing laboratories follow stricter protocols.
“No test is accurate every time you do it,” says Erika Ramos, genetic counselor and president of the National Society of Genetic Counselors. She works for Illumina, a company that makes sequencing technologies for clinical tests but also partially owns the DTC Helix testing service. Different types of testing deal with these potential errors in different ways.
Most DTC services use a strategy that tests most of your DNA very cheaply: up to a million different points. 23andme says that if it describes the condition formally in the report, it is a result that has been “tested and verified by QC,” and that in order to obtain FDA approval for some of their tests, they had to prove their methods were “over 99 percent” accurate. However, even a very low error rate is likely to cause multiple SNPs to be incorrect.
But 23andme makes no guarantees, especially regarding other results in your raw data. In fact, they include a disclaimer when uploading data stating that they have not been tested for accuracy and “are only suitable for research, educational and informational purposes and not for medical, diagnostic or other purposes.”
(In a recent study, no companies were named, so we don’t know for sure if the raw data came from 23andme. However, they are a very popular service for this type of testing.)
Clinical trials are more thorough. Instead of looking at SNPs across the entire genome, the lab will often read the entire sequence of one or more genes you asked about. They also do additional tests to find out if the corresponding section of your DNA has been removed or duplicated. And the lab will double-check their work if the initial results are questionable.
Despite all this extra effort, tests can be expensive. Ambri says their price list is between $ 200 and $ 1,500 for people who pay in cash, but that the average cost for someone with insurance is “under $ 100.”
Interpretation issues
Errors in the data explained only a few of the false positives in the Ambry study. Others proceeded from a difference in interpretation: if you have a certain variant at a certain place in your DNA, what does that mean for your health?
This is a tricky question because some SNPs can be controversial. Some of the false positives in the study were due to the DTC citing the result as increasing the risk of cancer or human disease, but Ambri considers this option harmless. You can see a table of these options here , as well as how they are classified in various publicly available databases.
If you’re playing along at home, consider doing a little research on the options in your DTC or third-party report. Stephanie Connor, lead author of the analysis, says ClinVar is a good place to test the variation you see in your raw data. It lists interpretations from different laboratories, even if they disagree. (The laboratories themselves are using this database to see how other interpretations are given and to try to figure out what they should really be telling patients.) She also suggested the HGMD and LOVD .
What to do if a genetic test received in the mail gives a terrible result
First, don’t panic. Whether the test comes back positive or negative, the tests sent in the mail will not tell the whole story of your genetics, let alone the full picture of your risk for the disease. Remember, your family history and other risk factors should also be part of the discussion.
If a DTC or third-party test shows that you have an increased risk of something like cancer, you can tell your doctor about it. However, not every doctor understands the difference between DTC tests and clinical trials. (Connor says he should , but she’s met some who don’t.)
Another way to get advice is to speak directly with a genetic counselor. You can find on findageneticcounselor.com those who are near you or who are available by phone. Select Home / Direct With the Consumer DNA Testing to find someone who will interpret and process these results. They can help you figure out if you need additional testing and how to get it.