Navigating incidental genetic findings for CVD requires caution, established framework
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Key takeaways:
- Incidental findings of genetic variants that indicate CVD risk should be interpreted with caution.
- A new statement highlights careful communication with patients and working with a multidisciplinary team.
Genetic variants associated with CVD found incidentally during testing should be interpreted with caution using a framework that includes a multidisciplinary team of experts, according to a new scientific statement.
“There has been a tremendous expansion in our ability to interrogate the genome for the causes of disease,” Andrew Landstrom, MD, PhD, associate professor of pediatrics and cell biology at Duke University School of Medicine, told Healio. “It is increasingly routine for clinicians to order exome sequencing or genome sequencing as part of a medical evaluation, particularly for sick infants and children, to identify the cause of disease that is otherwise challenging to diagnose. There has also been a significant increase in large population-based research initiatives that correlate exome and genome sequencing results to health outcomes, as well as increased access of the general public to direct-to-consumer genetic testing. All of these have led to an increase in the number of genetic variants that are found incidentally yet may carry disease risk, which could impact the health of the individual. The goal of this statement is to guide the physician or the researcher in how to interpret these variants when they fall in genes that are associated with the development of CVD.”
Avoid reporting ‘uncertain’ associations
The new American Heart Association statement, published in Circulation: Genomics and Precision Medicine, is the first to focus on inherited monogenic or single-gene diseases for CVD such as hypertrophic cardiomyopathy or long QT syndrome. The researchers note that health care providers should only relay information about CVD-associated variants to patients for genes that are already known to be associated with CVD; those with an “uncertain association” should not be reported.
Landstrom said there are several considerations when interpreting incidentally identified variants in CVD-associated genes.
“First, if the patient agreed before gene testing to learning about any incidental results, only incidentally identified variants predicted to be associated with CVD should be communicated to the patient,” Landstrom told Healio. “Second, the initial interpretation of a variant as CVD-associated is not always accurate, and this assessment can change.”
Establish a framework
The statement notes that clinicians and researchers should establish a framework for the interpretation of incidentally identified variants in CVD-associated genes that includes a patient-specific comprehensive CV evaluation; a reevaluation of the variant/gene association with the CVD in question; and determination of the risk for the variant being associated with disease development.
“This framework determines appropriate clinical management and follow-up of the patient and their family,” Landstrom said. “This framework should be conducted at, or in partnership with, a center specializing in heritable cardiovascular disease through a multidisciplinary team-based approach.”
Landstrom said researchers must continue to refine tools that allow clinicians to predict whether an incidentally identified variant may ultimately cause disease in people and, if it does, how severe the disease manifestation will be.
“There are emerging tools with tremendous promise for advancing researchers to this goal, including methods like artificial intelligence and the creation of large population-based databases of genomic data, as well as new experimental models that can allow us to learn more about disease development in the research lab,” Landstrom told Healio.
For more information:
Andrew Landstrom, MD, PhD, can be reached at andrew.landstrom@duke.edu; Twitter: @aplandstrom.
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