Genetic counseling and direct-to-consumer (DTC) genetic testing have co-existed for two decades, and by 2022, one in five Americans completed a mail-in genetic test [1]. Currently available DTC reports have relevance to every specialty in which genetic counselors practice, including preconception/prenatal care, oncology, cardiology, neurology, nephrology, and primary care. Despite the parallel evolution of the genetic counseling and consumer genetics fields, misconceptions about DTC—including ideas about the accuracy, clinical relevance, and role of DTC testing—persist.

As two genetic counselors within a DTC testing company working to increase access to genetic testing, we are ready to address some of these misconceptions.  Asking about and reviewing DTC genetic testing reports is not yet standard of practice for many genetic counselors, but we argue it should be. DTC genetic testing can be an accurate and clinically relevant part of a genetic risk assessment that also has the potential to expedite a diagnosis and change the course of medical management, for an individual and in some cases for an entire family.

Accuracy

The truth is, many of the DTC reports your patient might bring into clinic use the same technology, equipment, reference datasets, and data interpretation methods as genetic tests considered clinical grade. Some but not all DTC genetic testing reports are authorized by the Food and Drug Administration (FDA), meaning that they are subject to additional regulatory oversight and as a result have accuracy proven to rival that of any clinical lab.

Most clinical genetic tests, like a hereditary cancer panel or cell-free DNA screen, are not currently required to submit for premarket review by the FDA (as of the time of publishing). In contrast, FDA-authorized DTC genetic testing reports must meet high standards for analytical validity and clinical validity (including greater than 99% accuracy and greater than 99% reproducibility) as well as user comprehension [2].

Clinical Relevance

            DTC genetic testing may bring a person to clinical genetics services who might never have sought genetics care otherwise. For example, consider a woman in her mid-fifties whose DTC report states she has a variant detected in TTR who presents to a medical genetics service. Confirmatory testing confirms a genetic diagnosis of TTR-related hereditary amyloidosis, a notoriously hard to diagnose disease that affects as many as 1 in 28 individuals in certain populations [3,4]. The individual is found to have early manifestations of amyloidosis and is placed on TTR tetramer stabilizers. In this way, DTC testing operates like population genomic screening, providing an unselected group of individuals with access to genetic results at a scale that would be impossible within a traditional clinical model.

DTC genetic testing can also influence the counseling that is provided at genetics consults. Consider a woman in the first trimester of her pregnancy whose FDA-authorized DTC report notes that she has a variant in SLC37A4 associated with Glycogen storage disease type IB. After genetic counseling, the woman and her reproductive partner elect a carrier screening panel that includes SLC37A4. They opt for concurrent—as opposed to step-wise—carrier screening for the reproductive partner, given that the woman is almost certainly a carrier. In this scenario, DTC genetic testing plays an essential role in personal decision-making and clinician counseling.

Part of an Overall Risk Assessment

No genetic test, including DTC genetic testing, is standalone, and no genetic test provides an individual with a comprehensive genetic risk assessment. A positive finding on a hereditary cancer panel should be contextualized within a personal and family history gathered by a healthcare professional trained in genetics before any decisions on cancer surveillance are made. Carrier screening should be offered alongside prenatal aneuploidy screening and diagnostic testing and contextualized with fetal ultrasound findings.

         Genetics professionals regularly synthesize information from all parts of a case. DTC genetic testing is another essential tool in the growing toolbox that includes cancer pathology, family health history, physical exam, and many other clinical genetics risk assessment tools. Moreover, genetic counselors should utilize all available genetic information in their risk assessment; a risk assessment that discounts a patient’s highly validated DTC genetic testing reports is an incomplete one.

Addressing DTC Genetic Testing in Clinic

During a busy clinic day, genetic counselors have precious little time with patients. Your authors, who have spent a combined seven years within busy reproductive genetics clinics, are no strangers to this. A few suggestions that genetic counselors can implement to streamline integration of DTC genetic testing into their practice:

1. Integrate a question about DTC genetic testing in an intake form.
2. Request that a patient share a copy of their DTC report beforehand for review.
3. Acknowledge patient motivations for testing and ask about unexpected findings.
4. Note which DTC genetic testing labs and reports have undergone FDA premarket review and received FDA authorization, which includes requirements for analytical and clinical validity.

DTC genetic testing has evolved in leaps and bounds in the past two decades with greater innovation, regulation, and research. Hesitations to support and integrate DTC genetic testing into patient care may be based on outdated experiences. Genetics professionals can learn from engaging with consumer genetics, perhaps by undergoing testing themselves. DTC genetic testing is here to stay, and it offers a unique opportunity to improve and innovate patient care.

You can learn more at https://medical.23andme.com/ or reach out to us at medical@23andme.com.

References:

1. Orth, T. (2022, February 25). DNA tests: Many Americans report surprises and new connections. YouGov. https://today.yougov.com/society/articles/41232-dna-tests-many-americans-report-surprises-and-new-?redirect_from=%2Ftopics%2Fsociety%2Farticles-reports%2F2022%2F02%2F24%2Fdna-tests-many-americans-report-surprises-and-new-
2. Center for Drug Evaluation and Research. Direct-to-consumer tests. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/in-vitro-diagnostics/direct-consumer-tests
3. Yamashita, T., Asl, K. H., Yazaki, M., & Benson, M. D. (2005). A prospective evaluation of the transthyretin Ile122 allele frequency in an African-American population. Amyloid, 12(2), 127-130.
4. Carry, B. J., Young, K., Fielden, S., Kelly, M. A., Sturm, A. C., Avila, J. D., ... & Regeneron Genetics Center, Tarrytown, New York, USA. (2021). Genomic screening for pathogenic transthyretin variants finds evidence of underdiagnosed amyloid cardiomyopathy from health records. Cardio Oncology, 3(4), 550-561.

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