LOUISVILLE, Ky. – In recent years, health care leaders have sought to pave the way for personalized, predictive medicine by making genetic testing broadly available in physicians’ offices. However, multiplex genetic testing could overwhelm physicians with too much information and a significant commitment of time and resources unless policies for managing incidental findings are developed, according to a new article in Genetics in Medicine by University of Louisville pediatrician Kyle B. Brothers, M.D., and a team of researchers at the Vanderbilt University Center for Biomedical Ethics and Society.
Incidental findings are often unknown disease possibilities; for example, a genetic test performed to determine the best dose for hypertension medication could also reveal a possible risk for developing other conditions, such as different kinds of cancer.
Interpreting data is time intensive and requires sophisticated computer software and an electronic medical record, plus physicians need to spend significant time explaining test results to patients. Some providers may fear liability for failing to address all incidental findings. Furthermore, follow-up testing on incidentally-identified risks could become very expensive for patients and create unnecessary anxiety, given the inevitability of false positive results.
“Genetic tests generate more information than we know what to do with, so, much of that important, useful information could easily be overlooked,” said Brothers. “Instead of jumping in with both feet, we should think about the best way to approach what we call the ‘incidentalome’ (a potentially voluminous collection of incidental findings) so that patients can actually benefit from the best of this new knowledge.”
Mapping the incidentalome
The goal of this project was to characterize the incidental findings generated through multiplex genetic testing, which could include new technologies such as whole genome sequencing. The researchers used data from Vanderbilt University’s Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment (PREDICT) program, which tests 34 genes that can affect drug selection and dosing. They quantified the incidental findings with a comprehensive literature review of recent articles that referred to at least one of the 34 genes.
The researchers identified 372 associations between the genetic make-up and actual physical traits and health conditions that might be revealed in patients undergoing genetic testing to guide drug therapy for a specific condition.
“Ours was the most comprehensive attempt to ‘map’ the incidentalome so far. We looked at just 34 genes and found more incidental findings than providers and patients could handle. The human genome contains more than 20,000 genes, so we can say with confidence that providers and patients are going to need help handling this information,” Brothers said.
Only two previous studies have explored the incidental findings of multiplex genetic testing. This study, the largest to date, provides an updated and more comprehensive account of the number of genotype-phenotype associations generated through pharmacogenomics testing.
Beyond the incidentalome
Brothers is following this study with a similar one that measures the incidental findings per individual patient. “The FDA says we should be doing genetic testing before prescribing certain medications, but it has been very difficult to develop a process for applying this knowledge and integrating it into routine care. These studies are important steps in developing that process.”
He also is collaborating on a study of genetics and intellectual disability and is planning to explore the motivational effects of genetic testing for extreme obesity.
In 2013, Brothers will complete a Ph.D. in religious studies with a focus on medical ethics from Vanderbilt University, where he practiced pediatric medicine for eight years.
Brothers joined the UofL Department of Pediatrics faculty this summer. He conducts research on the translation of genomics into routine pediatric care and ethical challenges in the care of children. He collaborates closely with the university’s Kosair Charities Pediatric Clinical Research Unit, where researchers study drugs for children, including treatments that are based on the individual’s own genetic make-up. He also works as a general pediatrician in the UofL Physicians-General Pediatrics Broadway office and has a special interest in obesity.