How should these changes be communicated, how often, and who is responsible for this? The authors of this paper in BMC Medical Genomics discuss the topic further in this blog post.

A case of genetic testing

Samila* had been suffering from shortness of breath and exhaustion when, at the age of 19, she was diagnosed with a heart that did not pump properly. Attempting to understand what caused this condition, her cardiologist suggested genetic testing. The test showed no underlying genetic factors for her heart issues and her medication was so effective that Samila thought it all might have been a fluke. However, when she was 26, her cardiologist unexpectedly contacted her with some upsetting information: part of her DNA had been identified as being involved in the development of dilated cardiomyopathy.

*Fictionalized case

Genetic testing: uncertainty amidst possible expectations of certainty

A genetic test inspects parts or even the entirety of the genome, which contains all our hereditary information encoded in the DNA.

The field of human genetics studies the workings of human genomes and how variations within it might play a role in the development of medical conditions. Through these studies, our genes can offer us important insights into why we have developed certain conditions, whether we could develop them in the future, and whether our children are at increased risk of developing them.

We frequently attribute a great deal of certainty to genetic testing and the information it produces in terms of what it can tell us regarding current and future health risks. However, for all our expectations, the connection between our genes and discuss our health is anything but clear-cut. The information provided by genetic testing often contains a multitude of uncertainties.

One such uncertainty is that the meaning of genetic information can change over time. Depending on the moment a genetic test is performed or its data interpreted, patients may receive different results. This can be unsettling for patients and pose a real challenge to genetic professionals.

Stable genomes, changing understandings

People change, their genomes do not. Our genome is inherited at conception and generally stays constant beyond the day we die. Patients like Samila may, therefore, wonder why they receive new genetic information many years later after their DNA was initially “cleared”. Despite its fixed nature, our understanding and interpretation of the genome is anything but stable.

Genetic testing enables us to inspect an individual genome for variations that differ from a template (i.e. ‘the’ human reference genome). Everyone has millions of variations that differ from this reference, but most are harmless or even beneficial. For patients, then, we need to establish whether these variations can explain or predict conditions or whether they are innocent.

In this sense, geneticists are kind of molecular detectives. They uncover evidence in order to ascertain whether their “suspects” – i.e. variations in an individual’s genome – are guilty or innocent regarding the development of specific conditions.

Complicating the task of reviewing evidence, like in an actual criminal investigation, is that new evidence might unfold as time passes. This new evidence may redefine how genetic variation might be involved in medical conditions.

In Samila’s case, for instance, it was uncertain if some of the initially identified genetic variation was harmless or suspicious. But as time went on, more patients with the same condition appeared to have this genetic variation, which indeed could be associated with cardiomyopathy.

New evidence: important implications for patients

Evolving genetic evidence can have significant implications for patients and their relatives in terms of treatment decisions, medical protocols, and life decisions.

In Samila’s case, this new interpretation indicated a chronic heart condition that was likely to progress, irrespective of any treatment. Samila was advised to look for a job that was not too stressful. Her children have a 50% chance of having the genetic variation, putting them at higher risk of developing a similar condition.

Challenges for professionals in genetic healthcare

New genetic technologies produce information regarding genetic variation at unprecedented rates, continuously providing new data on the relationship between genetic variation and medical conditions as time moves on.

The changing nature of genetic knowledge raises highly challenging questions for professionals.

For instance, a laboratory geneticist’s role is to interpret the meaning of genetic variation. What are their responsibilities with respect to identifying and providing up-to-date, important health information to individuals who have been tested in the past?

If laboratories would enact a policy of routinely inspecting all new evidence and update the interpretation of genetic data in their registry, patients such as Samila could receive vital medical information at an earlier time. Samila might then have considered measures to prevent her children from inheriting the genetic variation.

However, the workload for professionals to review massive amounts of new evidence is exorbitant and would strain resources, potentially cutting into time spent on other healthcare-related activities. Should the responsibility therefore lie with Samila or her primary care practitioner to regularly request updated interpretations?

It is crucial that these issues are explored through research that includes the perspectives of those involved. Our study looks at these questions in the context of the genetic laboratory. We invite everyone interested to read this paper, which raises important points of consideration for clinical genetics practice.