Study: Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations

Contents

STUDY AT A GLANCE

Direct-to-consumer (DTC) tests, as the name implies, are genetic tests that a consumer can request directly from a company without involving a doctor or healthcare professional. DTC genetic tests are available for looking at common traits, making health predictions (e.g. presence of particular mutations for cystic fibrosis or sickle cell disease) and for ancestry analysis. In all cases, confirmation of any results by a clinical laboratory is needed to ensure that information is correct before any medical conclusions are possible.

More recently DTC genetic tests for determination of the presence of the 3 Jewish founder mutations in BRCA1 and BRCA2 have been made available. Note, this study evaluated DTC genetic tests that were done before 23andMe's more recently approved DTC test for the 3 common Jewish founder mutations was available. The quality of the test for the 3 common Jewish founder mutations was evaluated and approved by the FDA.

This study highlights the need for clinical validation of DTC genetic testing to confirm results and to ensure appropriate interpretation of results.

This study is about:

A clinical laboratory's evaluation of direct-to-consumer (DTC) tests and associated raw data analysis.

Study findings: 

The FDA allows direct-to-consumer genetic testing for ancestry analysis, raw data, and limited clinical testing (including the 3 common Jewish BRCA mutations). These genetic tests come with a clear warning that any potential clinical variants must be reconfirmed by testing in a clinical laboratory.

Researchers at Ambry Genetics, a private clinical testing laboratory found that many mutations reported by DTC testing were absent (false positive) or misinterpreted.

• 40% of mutations (17 of 43) identified by DTC or subsequent third-party analysis of raw data were false positives: testing new samples showed that the individuals involved did not carry these mutations.
• Among mutations present, 8 that were classified as having "increased risk” by DTC or third-party providers were known to be benign, common variants or of unknown significance.

We note that this study predated the recent FDA approval of DTC testing for 3 common Jewish mutations in BRCA1 and BRCA2 (see prior XRAYS review). DTC testing for the 3 common Jewish mutations has met FDA standards for accuracy and reliability; these tests were correct and were not the type of tests examined by this study. Some DTC genetic tests (e.g. ancestry analysis) provided consumers with whole genome raw data. This raw data includes DNA sequence from regions that may have poor sequence quality or insufficient information. These regions would not be appropriate to determine presence or absence of a mutation (and are therefore not intended for clinical use).

What does this mean for me?

If you have had or are considering DTC genetic testing, be aware that the information provided is not intended for clinical diagnosis or risk assessment. All potential mutations found via DTC testing need to be reconfirmed by a clinical diagnostic laboratory. This study highlights the high potential rate of false positives—DTC results that incorrectly stated that individuals carried a mutation when they did not. These erroneous results can be a technical limitation of the DTC tests and analysis of raw data. Tests to reconfirm the presence or absence of these mutations are needed before this information can be used for clinical decisions.

The misinterpretation of some mutations as "increased risk" rather than benign mutations, which frequently occur in the population and are not associated with disease risk, points to the need for adequate genetic counseling from a certified genetic counselor or other trained health care professional.

It is important to know that DTC testing is typically not comprehensive. It may include only some and not all genes for a disease, and it may not test for some mutations in all regions of individual genes. Clinical laboratory testing is more comprehensive for a given disease or gene tested. FORCE recommends consulting a genetics professional (such as a board certified genetic counselor, medical geneticist or other provider with advanced training in medical genetics) before and after being tested so that the appropriate test is performed and properly evaluated. If DTC testing is pursued, it is important to bring any test results to your health care provider so you can discuss what you have or have not had tested and to ensure a complete understanding of your genetic tests.

Posted 6/26/18

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References

Tandy-Connor S, Guiltinan J, Krempely K, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. 2018.Genetics in Medicine. Advanced online publication March 22, 2018. doi: 10.1038/gim.2018.38.
 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.