Direct-to-Consumer Genetic Testing FAQ

Direct-to-Consumer Genetic Testing for Healthcare Professionals

What is direct-to-consumer genetic testing?

Direct-to-consumer genetic tests (DTC-GT) are genetic tests sold directly to consumers to provide information about their genetic information (generally ancestry, some health traits and health risks) from a saliva sample. Ordering and return of results for DTC-GT typically does not involve health care professional engagement or the use of health insurance to cover the cost of testing. MedlinePlus Genetics gives an overview of DTC-GT for patients.¹ 

Presentation by the ISCC-PEG DTC-GT Project Group

What are other types of genetic testing?^2,3

Three main categories of genetic testing are currently available: Clinic-based, direct-to-consumer, and provider-mediated genetic testing (see table 1). Clinic-based genetic testing is ordered, interpreted and disclosed by a physician or other healthcare professional through a traditional healthcare professional-patient relationship. Standard-of-care approaches to clinic-based genetic testing involve a pre-test consultation to identify and document potential genetic risk factors, select the most appropriate test, and discuss the benefits and limitations of testing to facilitate informed consent from the patient. During a post-test visit, test results are disclosed and interpreted. 

In recent years, multiple types of genetic testing products marketed directly to consumers have emerged. Compared to direct-to-consumer genetic tests (DTC-GT), provider-mediated genetic testing (PM-GT) engages a healthcare professional in a non-traditional role as part of the testing process. The professional’s involvement may be limited to placing the test order or approving the order for genetic testing with minimal interaction or discussion of the test with the consumer. This professional may be employed by the company that conducts the genetic test and may not know the consumer, or the healthcare professional may already care for the consumer.² 

Table 1: Types of genetic testing

Milestones in the Timeline of DTC-GT:
 

• 1996: A UK genetic testing company launched mail-order genetic testing. In the United States, genetic testing companies marketed BRCA gene testing directly to consumers via newspapers.
   
• 1998: A clinical genetic testing company launched a consumer advertising campaign on television, on radio and in magazines.
   
• 2001: A nutrigenetics company in the United Kingdom marketed genetic tests to consumers directly via their website. 
   
• 2003: The Human Genome Project was completed. 
   
• 2005: The first DTC companies were founded. 
   
• 2006: The US Government Accountability Office (GAO) investigated DTC-GT companies.
   
• 2010: GAO released a report indicating that these companies made medically unproven disease predictions.
   
• 2007: DTC-GT was offered at $1,000. 
   
• 2010: The Food and Drug Administration (FDA) initiated regulatory proceedings against DTC-GT companies. 
   
• 2012: DTC-GT prices dropped to $99. 
   
• 2013: The FDA sent cease and desist letters to DTC-GT companies. In response, some DTC-GT companies elected to end their testing services. Others modified their products as instructed by the FDA, then worked closely with the FDA to ensure that existing and newly developed testing products met their standards.
   
• 2015: The FDA approved DTC-GT carrier screens. 
   
• 2017: The FDA approved DTC-GT for certain health-related conditions. 
   
• 2018: more than 26 million consumers had contributed their DNA to commercial databases. 
   
• 2020: the FDA granted a DTC-GT company clearance for a pharmacogenetics report for interpretive drug information for two medications — clopidogrel and citalopram — removing the need for confirmatory testing.
   

What are the benefits of DTC-GT from a healthcare standpoint?

While DTC-GT does not test for most genetic traits or diseases, DTC-GT can provide information about potential risk for some genetic conditions or for being a carrier for certain genetic diseases. Knowing this information can remove some of the fear and stigma that may be associated with genetic testing and with discussions around family health history. 

Some DTC-GT options can give consumers a better sense of personal health agency, allowing for a more proactive approach to their health. After people share their DTC-GT results with their healthcare professionals, they may be motivated to consider the professionals’ screening and intervention recommendations.

DTC-GT often provides results for specific variants more quickly and can be less expensive than some clinical genetic tests ordered through a healthcare professional. This is especially true in cases where people do not have adequate health insurance or established relationships with healthcare professionals, and are concerned about waiting times. Testing is non-invasive and does not require a blood draw. 

Consumers are not required to share their results from DTC-GT with their insurance professionals, which offers an additional level of privacy. In some cases, a consumer’s desire to be a part of research is a motivator to have DTC-GT because they can opt into research studies being performed by the DTC-GT company.

What are the limitations of DTC-GT?

One of the major limitations of DTC-GT is that it often does not test for all pathogenic or disease-causing variants for a particular condition, so the results cannot be used to rule out a condition. In addition, some consumers may be interested in a particular condition that DTC-GT does not cover. Even if DTC-GT shows a potentially actionable result (e.g., a test detects a BRCA1 pathogenic variant), these results need to be confirmed with a clinical genetic test; therefore, DTC-GT may add an unnecessary step to the process, as well as additional time and cost. 

Some DTC-GT companies may test for conditions or traits that do not have confirmed clinical utility or have no confirmed gene to phenotype correlation (e.g., genetic testing to see which vitamins a person should take).

Another limitation is that DTC-GT is often completed without traditional genetic counseling, risk assessment or informed consent to confirm that the consumer fully understands the implications of the possible results. DTC-GT may give patients data that are overwhelming, non-actionable or distressing without the support of a qualified healthcare professional.

For ancestry results, DTC-GT may reveal a genetic relationship to biological relatives that is unexpected and possibly distressing. These tests may uncover ancestral origins that may be previously unknown. In addition, the databases of DTC-GT companies do not cover all ethnic populations equally; therefore ancestry results for underrepresented minority populations may be inaccurate. 

More recently, some DTC-GT companies have been in the media for allowing law enforcement to access their databases to solve crimes.⁷ As a result, consumers may have privacy and safety concerns. Additionally, depending on the DTC-GT company, an individual’s DNA may be used for research or commercial purposes, and consent for each use may not have been expressly given or understood. 

Do the methodologies for DTC-GT and clinic-based testing differ?

DTC-GT for health conditions and carrier status is often performed by single nucleotide polymorphism (SNP) arrays (See How does DTC-GT use SNP arrays?) A few types of DTC-GT also use next-generation sequencing, but these are for more specialized tests. In contrast, DTC-GT for ancestry uses SNP arrays, short tandem repeats (STR) testing or region sequencing. Many of the DTC-GT used today in 2021 only look at a small slice of a person’s genomic information to make estimates about certain health traits, risks or ancestry. 

Clinic-based genetic testing typically involves more thorough genetic testing methods including SNP arrays, next-generation sequencing, copy number analysis or methylation analysis. The methodology used depends on the genetic condition. Results are confirmed and interpreted by the clinical lab within the context of published medical guidelines and by the healthcare professionals with consideration of the patient’s personal and family health history. 

Even when DTC-GT uses more comprehensive methodologies, the test reports only include a predetermined set of variants.

Clinical genetic testing labs must have established quality standards, such as Clinical Laboratory Improvement Amendments (CLIA) certification and College of American Pathologists (CAP) accreditation. Although a few DTC-GT companies do have these credentials, they are not required to have them. Some DTC-GT labs may have FDA approval, but the FDA states, “Results obtained from the tests should not be used for diagnosis or to inform treatment decisions. Users should consult a healthcare professional with questions or concerns about results.”⁸

DTC-GT is often performed by SNP array. What kind of results do SNP arrays in DTC-GT provide?

The number and location of tested SNPs varies among DTC-GT companies. Some of the SNPs on the array have clinical relevance and may be used to establish carrier status for genetic conditions. Other SNPs may suggest genetic conditions or health risks in the tested individual or may be relevant for medication selection and dosing.

Certain SNPs on the array are used to determine a person’s ancestry. Differences in SNP frequencies between groups with different ancestry can help track the human family tree. Computer algorithms analyze a consumer’s SNP results and determine the most likely ancestral origin for each section of the DNA. With 100,000 to 1 million markers, these estimates are usually accurate, but they rely heavily on pre-existing data. Minority populations may be mis-identified by DTC-GT if DNA sequences from their group are not available for comparison.

DTC-GT and Adopted Adults

What if my patient is adopted or has little family history?

Adoptees often do not have records or knowledge of genetic family health history due to either missing or untranslated records in intercountry adoption or lack of access to birth records in domestic adoption. Even if an adoptee has contact with a biological relative, their contact may be sporadic and the adoptee may not be able to piece together a complete family health history.

The use of DTC-GT is one of the few ways adoptees can open doors to their genetic health history. While not a traditional care model, DTC-GT allows adoptees a way to begin to understand their genetics and take action based on their results. These results are often the only glimpse that adoptees have of their biological makeup and can be meaningful to them even if their results are inconclusive.

How do I handle DTC-GT results for an adoptee?

If an adoptee is found to have a positive carrier test result, disease risks or other health result, consider referring them to a genetic counselor or a genetics professional.

A genetics professional will discuss clinical genetic testing to confirm if variants are pathogenic and address potential risks, if any. The adoptee may be offered education, increased screening, treatments and interventions as appropriate. 

Results from DTC-GT may have an impact on adoptees and their biological relatives, if any are known. Healthcare professionals are encouraged to discuss how DTC-GT results may affect biological children or close relatives. A discussion on relatedness and inheritance may also be appropriate, as DTC-GT may reveal distant relatives. 

Preconception or prenatal testing can be considered if the adoptee desires to be or is pregnant. They may want to consider seeing a prenatal genetic counselor or other genetics professional to discuss the results of their DTC-GT, consider clinical genetic testing to confirm results and review inheritance and risk to a pregnancy. 

What if an adoptee is considering DTC-GT for health information? 

If an adoptee does not meet criteria for clinical screening or medical interventions based on personal health history and is motivated to explore genetic testing for hereditary conditions, consider referring them to a genetic counselor or genetics professional to discuss clinical genetic testing and patient self-pay options.

In addition, consider discussing the limitations of DTC-GT for health information; if adoptees test negative for disease risks and health results via DTC-GT, they may have a false sense of security because they may carry a pathogenic variant not included in DTC-GT. If they test positive for a genetic variant related to disease, they should confirm these results with clinical genetic testing. 

What if my patient was conceived using donor eggs or sperm and wants to use DTC-GT to obtain health information?

DTC-GT is not comprehensive and should not be used to obtain health information. DTC-GT results may also violate donor agreements for anonymity. Instead, consider referring the patient to a genetic counselor or other genetics professional to discuss carrier screening or genetic testing for hereditary conditions. 

Many donor banks screen eggs and sperm for common hereditary conditions, but not all companies test for the same ones and the tests are not considered comprehensive or clinically validated. If a patient is interested in their past screening, consider recommending that they reach out to their donor egg bank or sperm bank to discuss what genetic screening or testing was performed.

DTC-GT Raw Data, Third-Party Interpretation Services and Data Privacy

What should I tell my patient about raw data from direct-to-consumer genetic testing?

Raw data refers to the data file consumers may receive from their DTC-GT company. The data file consists of uninterpreted genotype information.² Many of the variants in a consumer’s raw data are used for research by the DTC-GT company and often do not have enough data to classify any variant as pathogenic. However, consumers are curious about their raw data and may upload their raw data files to third-party interpretation services to help interpret the data.¹⁹ Using raw data to obtain additional analysis through third-party interpretation services can yield false positive results; results should be clinically confirmed before making any healthcare decisions. MedlinePlus Genetics provides excellent information about DTC-GT raw data.²⁰

Third-party interpretation services ²¹

1. High risk for false positives: Some of the third-party interpretation services claim to give consumers more details about their disease risks and traits.²² However, many of these services have provided false positives and unexpected information, both of which can cause unnecessary distress to consumers.
    
2. Privacy concerns and few regulations: One of the most significant concerns with third-party interpretation services is the lack of informed consent and inconsistent privacy measures.^21,23 Law enforcement has been known to search third-party databases for distant relatives of suspected criminals in order to locate the suspect.⁷ Additionally, there is little regulation of these services.
    
3. Raw-data results still need clinical confirmation: If patients bring their raw data report to a healthcare professional, consider referring them to a genetic counselor or other genetics professional to discuss their findings and consider clinical genetic testing to confirm a suspected pathogenic variant. 

How do direct-to-consumer genetic testing companies protect customer privacy? 

The ways in which DTC-GT companies protect consumers’ privacy vary.²⁰ Consumers should be aware of how the companies protect their genetic information and personal identifiers, and they should check to see if their genetic information might be used for research or advertising. Privacy policies and statements are located on the testing companies’ websites, but consumers may require time and assistance to find and understand the policies. For more information on privacy concerns, visit MedlinePlus Genetics.²⁰

Costs of Genetic Testing

How much does DTC-GT cost?

DTC-GT prices vary depending on how many variants are examined, the type of results offered and the structure of the test (e.g., ancestry only, health and ancestry, health only or analysis and consultation with a genetic counselor). The price can range from under $100 to thousands of dollars. Because DTC-GT results are typically not considered diagnostic, health insurance companies often do not cover the cost of the test.

How much does clinical genetic testing cost?

When needing to confirm a DTC-GT result with clinical genetic testing, the patient should find out whether their insurance provider covers clinical genetic testing. For example, a patient may not meet the national cancer guidelines that recommend who should be offered genetic testing based on personal and family history of cancer; as a result, their insurance provider may not cover the cost of clinical genetic testing. However, many large clinical genetic testing companies offer a self-pay option, less expensive rates and financial assistance programs.

If the patient meets genetic testing guidelines, their insurance may have a high deductible, which may make the cost of testing unaffordable. In this scenario, the self-pay option or financial assistance program from a genetic testing company may offer a lower cost for the patient. For more information on insurance and costs, please visit MedlinePlus Genetics.²⁶

Genetic Counselors and Other Genetics Professionals

Where can I find a genetics professional to refer a patient for a genetics consultation? 

The National Society of Genetic Counselors (NSGC) provides information on how to find a genetic counselor nationwide for consultation in person or by phone.

The American College of Medical Genetics and Genomics (ACMG) offers a search form by type of specialist patients may need.

The ACMG also has a Find a Genetics Clinic tool.

The Genetic and Rare Disease Information Center has a toll-free phone number to help patients find specialists: (888)205-2311.

Bibliography

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3. Chokoshvili, D., Vears, D. F. & Borry, P. Growing complexity of (expanded) carrier screening: Direct-to-consumer, physician-mediated, and clinic-based offers. Best Practice & Research Clinical Obstetrics & Gynaecology 44, 57–67 (2017).
    
4. Regalado, A. More than 26 million people have taken an at-home ancestry test. MIT Technology Review.
    
5. Allyse, M. A., Robinson, D. H., Ferber, M. J. & Sharp, R. R. Direct-to-Consumer Testing 2.0: Emerging Models of Direct-to-Consumer Genetic Testing. Mayo Clinic Proceedings 93, 113–120 (2018).
    
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7. Kaiser, J. We will find you: DNA search used to nab Golden State Killer can home in on about 60% of white Americans. Science (2018) doi:doi:10.1126/science.aav7021.
    
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12. Ramsey, L. B. et al. Prescribing prevalence of medications with potential genotype-guided dosing in pediatric patients. JAMA Netw Open 3, (2020).
     
13. Chanfreau-Coffinier, C. et al. Projected prevalence of actionable pharmacogenetic variants and level A drugs prescribed among US Veterans Health Administration pharmacy users. JAMA Netw Open 2, (2019).
     
14. Mostafa, S., Kirkpatrick, C. M. J., Byron, K. & Sheffield, L. An analysis of allele, genotype and phenotype frequencies, actionable pharmacogenomic (PGx) variants and phenoconversion in 5408 Australian patients genotyped for CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes. J Neural Transm (Vienna) 126, 5–18 (2019).
     
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20. How do direct-to-consumer genetic testing companies protect their customers’ privacy? MedlinePlus Genetics.
     
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22. Badalato, L., Kalokairinou, L. & Borry, P. Third party interpretation of raw genetic data: an ethical exploration. Eur J Hum Genet 25, 1189–1194 (2017).
     
23. Phillips, A. Giving away more than your genome sequence?: privacy in the direct-to-consumer genetic testing space. 36.
     
24. Genetic Discrimination. Genome.gov.
     
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27. Where can I read more about the diseases and traits covered in my direct-to-consumer genetic testing report? MedlinePlus Genetics.

The Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-PEG) provides a venue for individuals to collaborate and develop educational resources. The opinions expressed in this resource do not reflect the view of all ISCC-PEG members, the National Institutes of Health, the Department of Health and Human Services, or the United States government.