In people ordering genetic CV tests, positive result rate varies with age
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Among people who ordered a genetic test for dyslipidemia, younger people were more likely to have a positive result than older people, according to a presentation at the National Lipid Association Scientific Sessions.
Catherine Schultz, MS, CGC, specialty genomic science liaison at Ambry Genetics, presented results of a study on ordering trends and testing outcomes for more than 3,000 participants who underwent genetic testing for dyslipidemias at Ambry from 2014 to 2020.
“The clinical indication and utility of genetic testing is very well established, understood and recognized in not only the cardiovascular and lipidemia communities, but across the broader genetics community,” she said during the presentation. “This has been illustrated by the inclusion of familial hypercholesterolemia (FH) as a disease state, which should be reported as an incidental finding following exome sequencing or genome sequencing through recommendations from the American College of Medical Genetics. However, these monogenic dyslipidemias remain underdiagnosed and poorly recognized in patients, despite the wider acknowledgement in the genetics and cardiovascular communities.”
Participants were stratified based on whether their testing outcome was positive, negative or inconclusive.
Schultz said 31.42% of participants received a positive report.
“Targeted gene sequencing and single-site analysis had the highest diagnostic yield, indicating that a strong family history or very, very high clinical suspicion for that particular gene of interest was fueling this particular ordering trend,” she said. “We also saw that patients were receiving inconclusive results across the board, primarily in next-generation sequencing panels, allowing us to identify more than just a known targeted mutation. These patients had a variant of unknown significance, meaning that there is not significant evidence to classify that as either pathogenic in causing disease or benign. These particular types of variants require additional study.”
Although most participants were older than 36 years, “we saw a significant difference in patients under the age of 18 receiving a positive result,” Schultz said. “In looking at FH testing, we saw a negative correlation between a patient’s age and the likelihood of receiving a positive diagnosis (R2 = 0.9825). This can be explained by many different reasons. Primarily, we feel that patients with younger age undergoing testing are likely doing so due to a strong family history or known familial mutation that prompted cascade screening. Therefore, these patients have a much higher pretest probability of testing positive, at 50% based on recurrence, as opposed to patients in the more generalized screening population for dyslipidemias. Additionally, younger patients may be presenting to clinic with much more striking and severe disease states, prompting that referral, compared with older patients who may present with more general dyslipidemias that could be associated with genetic contributions or environmental factors.”
Among those who ordered a custom next-generation panel, 36.27% included at least one lipid gene, and of those, 31.69% included genes associated with other cardiac factors but not dyslipidemia, Schultz said, “indicating that patients may be undergoing genetic testing for more than one primary indication of some type of cardiovascular disease, or these providers are interested in knowing what the risk associated with a hereditary dyslipidemia may be.”
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Schultz C, et al. Late-Breakers & Partner Abstracts. Presented at: National Lipid Association Scientific Sessions; Sept. 24-26, 2021; Orlando, Fla. (hybrid meeting).
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