CHAPEL HILL – A growing number of Silicon Valley employers are offering genetic testing as a “cutting edge” benefit to employees, but a UNC-Chapel Hill genetics professor is not at all a fan of the practice.
“This is basically an uncontrolled experiment that is being done in healthy individuals, offering a genetic test that is clinically indicated for people with suspected cancer predisposition but far beyond the standard of care for the general population,” Dr. Jonathan Berg, an associate professor of genetics.
“Companies seem to be offering this in order to be ‘cutting edge’ or to provide their employees with something that differentiates them from other employers but is probably exposing their employees to potential harms without providing adequate pre-testing informed consent.”
Berg emerged as a critic of the practice in a story about the genetic testing wave published by The New York Times and reprinted by WRAL TechWire.
“There is exactly no evidence that systematic screening of the general healthy population for rare genetic conditions will have a net benefit in terms of health outcomes,” Dr. Berg told The Times.
WRAL TechWire followed up with Dr. Berg, who responded to a series of questions via email from a research conference is attending.
The story specifically mentioned two companies offering the genetic tests – Color Genomics and 23andme.
Asked if his concern was specific to Color Genomics, Dr. Berg replied:
“No, this concern is related to any population-based genomic screening. In my opinion, this is a topic that needs to be more carefully examined in a research setting before it is rolled out to the public.”
He said he had similar concerns about 23andme.
Dr. Berg has been deeply involved in genetics research and has been published in a variety of publications. He also has been part of teams that have presented “posters” about the topic at medical conferences. He also has a clinical appointment in the Department of Medicine, Division of Hematology-Oncology and the Lineberger Comprehensive Cancer Center.
Complexities of unraveling genetic meaning
To be clear, Dr. Berg is NOT dismissive of benefits that can be gained from continuing genetic studies. But he also doesn’t understate the complexities and challenges of genome research.
“Advances in genetics are coming at a breathtaking pace, but our ability to utilize this information clinically remains a significant limitation of genomic medicine,” says the website for The Berg Lab at UNC.
“To this end, I am leading one of the groups involved in a consortium effort called the “Clinical Genomics Resource (ClinGen)” that includes two NHGRI-funded U01 projects, an NHGRI-funded U41 project, and the NCBI’s ClinVar database. The overall goal of this consortium is to develop a publicly available knowledge-base of clinically-relevant genes and genetic variants, in order to facilitate the deployment of clinical genomics.”
Dr. Berg is also involved in the NCGENES [North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing] project which is a research study “evaluating whole exome sequencing (WES) as a diagnostic tool in a diverse group of patients with conditions likely to have a genetic etiology, but have evaded diagnosis by traditional methods.”
The Skinny reviewed a poster about the project and ask Dr. Berg how those findings contribute to your statement made to the NYT?
“This poster is about diagnostic findings in patients who have existing evidence of a health condition that might have an underlying genetic basis,” he explained.
“Basically, this is what we do clinically in Genetics Clinics across the country. It is quite clear that identification of a specific genetic etiology that explains an individual’s personal or family history of disease can be very useful clinically and (in some cases) lead to improved health outcomes and probably favorable health economic outcomes.
“However, this is completely different from testing in a general population that has a very low chance of having these conditions, and even if they are found to have a pathogenic variant in one of these genes the clinical implications are far from clear.”
That poster also clearly stated challenges remain, such as:
- Genome is big & all variation has not been discovered
- Large majority of variants will be VUSs [Variants of Uncertain Significance]
- Rare variants are frequent & difficult to assess
- Use of appropriate filters can help reduce the number of variants requiring analysis, thus limiting VUSs
Dr. Berg then noted another poster that he considers relevant to his point of view.
“Although it is a bit old now, the poster provides some of the basis for our concerns about screening in the general population,” he pointed out.
“This is essentially a statistical issue. Genetic tests are imperfect (as are all medical tests) and performance of those tests depends on the population being examined.
“Utilizing an imperfect test in a setting where the prior probability of disease is high can still provide relevant information, especially when coupled with clinical contextualization by a trained genetics provider (genetic counselor or MD geneticist); whereas the test performance will suffer greatly in a population where the prior probability of disease is relatively low, resulting in far more false positive results than true positive results.
“It’s just math.”
Meanwhile, Dr. Berg remains deeply involved in the NC genomics project.
“We have several large multidisciplinary genomic medicine projects that are too complicated to fully explain in a brief email,” he explained. As way of a brief summary, here’s his update:
- NCGENES – the initial phase of the study explored the use of exome sequencing as a diagnostic test in diverse patients with a broad range of suspected genetic disorders, with a focus on both primary and secondary/incidental findings.
- NCGENES 2 – the next phase of the study is a randomized controlled trial of exome sequencing versus usual care for diagnosis of suspected genetic disorders.
- NC NEXUS – an exploratory study of exome sequencing in newborns, addressing some of the complex ethical/legal/psychosocial issues about doing this.
- GeneScreen – this is actually the closest to studying the issues raised in the NYT article and examined the use of targeted sequencing for rare genetic conditions in healthy adults. You may wish to speak to Gail Henderson and Jim Evans, who were the PIs of that project, for more information.
At his website, Dr. Berg stresses why he is involved in such complex work.
“My research involves the application of next-generation sequencing for translational research projects including gene discovery, diagnostic testing, genomic medicine in healthy adults, and newborn screening,” he writes. “These projects are all intended to contribute to the knowledge base that will be required to make genomic medicine a reality.”
The work continues.