NEW YORK – With genome and exome sequencing tests becoming cheaper and readily accessible to people, the American Heart Association (AHA) is worried that incidental findings from these tests about cardiovascular disease risk are not being reported and communicated properly.
On Monday, the AHA, an almost century-old nonprofit organization, put out guidelines in its journal Circulation: Genomic and Precision Medicine on how incidental gene variants related to cardiovascular diseases, which are the number one cause of death in the US, should be interpreted and communicated.
Incidental variants refer to identified rare variants that are not related to the phenotype or disease presentation for which the testing was ordered, the authors noted.
"We are at this sort of inflection point where we're seeing more and more genome and exome sequencing being done in patients that are finding these variants in cardiovascular diseases," Andrew Landstrom, chair of the scientific statement writing committee and associate professor of pediatrics and cell biology at Duke University School of Medicine, told GenomeWeb. "There has been a lot of scientific debate about the best way to return these results to individuals," he added.
While direct-to-consumer genetic tests have become popular, clinicians are often not involved in their interpretation, according to the report. "Consumers are ending up with genetic findings that they're struggling with, and they are bringing these to their physicians to try to ask for guidance," said Landstrom.
The recommendation was based on guidance published by the American College of Medical Genetics and Genomics on 78 genes, of which 42 (54 percent) are inherited monogenic genes known to increase the risk of sickness or death from sudden cardiac death, heart failure, and other types of cardiovascular disease.
The guidance recommends that out of these genes, only the variants that are "pathogenic" (P) or "likely pathogenic" (LP) should be communicated to the patient. It also offers a scoring system to interpret the variants as P/LP.
The report strongly emphasizes that incidental findings should be communicated with patients only if they consented to receiving the information prior to the test.
Meanwhile, it adds that variants of uncertain significance should not be communicated with the patients at all.
As next steps, the variant should be re-evaluated at, or in close consultation with, a multidisciplinary center specializing in cardiovascular genetics, and other family members should be screened for the variant. "The goal of this evaluation is to determine whether the individual has evidence of the disease, such as symptoms or relevant test results, or if there are any warning signs in the family history," the report adds.
Landstrom said that the most important takeaway from this statement is that not every variant will end up causing disease. "That's where this framework is incredibly important — to be able to provide a comprehensive evaluation for the patient, and to give a probabilistic determination as to whether that variant may or may not cause disease," he said.