How direct-to-consumer genetic testing changes the conversation about health

Options for direct-to-consumer genetic or genomic tests, conducted without health professional’s oversight, are increasing. Helping patients to interpret the results of direct-to-consumer tests can be challenging but understanding patients’ motivations for using the tests can be illuminating.

What is direct-to-consumer genetic or genomic testing?

Direct-to-consumer genetic and genomic tests might examine single genes, like the cystic fibrosis gene (CTFR), look for variations (single nucleotide polymorphisms or SNPs) in thousands of different genes, or use whole genome sequencing. They provide information about ancestry, traits, health risks, hereditary diseases, or optimisation of diet or medication based on genetic information.

The term ‘direct-to-consumer genetic test’ (DTC-GT) is generally used to describe tests that are ordered, conducted and reported without involving a health professional.

Men’s use of DTC-GTs

Not much is known about men’s use of DTC-GTs. It seems that Australian males are less likely than females to have a ‘personal genomic test’¹, but US males are slightly more likely than females to have one (but are less likely to discuss their test results with a medical professional)².

Concerns about DTC-GTs

When DTC-GTs first became available, concerns were expressed about the capacity of genetic counselling services to meet the anticipated demand³. Over 10 years, 11 Australian clinical genetics services received 114 referrals resulting from DTC-GTs⁴. In the majority the referrer was ‘unsure of the significance of the DTC-GT results’.

Information supplied by DTC-GT providers is complex and difficult for many people to understand⁵. The ‘genetic literacy’ (the ability to understand and make use of genetic information)³ of consumers and health professionals is regarded as insufficient for dealing with DTC-GTs, resulting in recommendations for improved education⁶.

Even if DTC-GT results are understood, they may not be reliable. A small US study of requests for clinical testing to confirm DTC-GT results showed 40% of variants to be false positives⁷.

The clinical utility of DTC-GTs is limited in some instances by their narrowness, and in others by their breadth⁸. Of the thousands of genetic variants that affect health, DTC-GTs measure only a few, potentially missing some that influence disease risk. This can give the impression that someone has no genetic risk when in fact they do. The reference genomes used as the basis for comparisons might also be too narrow, making results irrelevant to people of different ancestry⁸.

The breadth of DTC-GTs can be problematic if variations are detected in genes that have only minor consequences for disease risk or lack evidence-based management strategies³. Knowledge that you possess a genetic variation that confers increased disease risk, but lacks effective treatment, can cause distress or harm from unnecessary screening and treatment. 

Australian regulations essentially prevent the provision of health-related information (limiting interpretations to ancestry and traits) but there are many “third-party interpreters”, who provide health-related information from ‘raw data’ downloads of test results. Two-thirds of people who have a DTC-GT in the US use a third-party service to interpret their raw data⁹. These services suffer from the problems of narrowness and breadth mentioned above, in addition to concerns about consent and data privacy¹⁰.

In purchasing a DTC-GT, consumers agree to share with the testing company their genetic information, which may be used for research, sold to third parties, and stored indefinitely, meaning that identifiable genetic information could be used for purposes not considered when people choose a DTC-GT. For example, the Golden State Killer, Joseph D’Angelo, was arrested in 2018 based on genealogy performed using public databases from DTC-GTs, which initially identified a distant cousin¹¹. D’Angelo may never have been identified without DTC-GTs, even though he never had one.

Practicalities of DTC-GTs

Healthcare professionals are concerned that people are misled and misinformed before choosing to undertake DTC-GTs¹², which is not surprising since counselling before and after clinical genetic tests is the norm.

Ideally, patients would discuss their intention with their general practitioner before undergoing a DTC-GT¹³. In these circumstances, GPs should ask¹⁴:
 

• How much does the patient understand about the test?
• What do they want to find out and what will they do with that information?
• Have they thought about the impact of testing on insurance?
• Will the company help interpret the results?
• Are you able to assist in interpreting results?
   

Helpful questions for patients considering DTC-GTs include¹⁵:
 

• Why do you want the test?
• If you receive a concerning result, does the provider of the test have people you can talk to about it and qualified people to advise you?
• Have you read the small print?
• Could having the test affect your family?
• Are you comfortable with how the test provider might use your genetic data?
   

If GPs are presented with patient concerns arising from a DTC-GT, it’s best to encourage and respond to questions¹⁶. Patients should be reassured that the predictive value is low when there is no family history of disease, and that false positives are common¹⁵.

If a patient presents with a ‘positive’ result for a disease-causing gene variant identified by a DTC-GT, clinical genetic testing is necessary only if early disease detection and/or treatment are available; not if variants are not ‘clinically actionable’¹⁵. In most cases, explaining of the limitations of the results and counselling the patient about lifestyle modifications that reduce disease risk is suitable^{15, 16}. Patients with ‘positive’ results and symptoms of disease should be investigated the same way as other patients without DTC-GT results¹⁵.

If health professionals know that patients have undergone a DTC-GT and received ‘negative’ results, it can be informative to enquire about their reasons for having the test in the first place. Some people may receive false negative results for heritable diseases that require more appropriate clinical investigations¹⁵.

DTC-GTs present an opportunity

Despite their limited clinical utility, DTC-GTs respond to people’s desire to take responsibility for their health and well-being. The conversations that emerge from patient enquiries about DTC-GTs can be illuminating for patients and health professionals, providing chances to discuss patients’ health concerns and ways to minimise risk and screen for disease.