NEW YORK (GenomeWeb) – A new study suggests that cardiomyopathy genetic tests are more adept at uncovering pathogenic or likely pathogenic variants in white patients than in patients from other ethnicities.
Researchers from the US Food and Drug Administration, Partners Healthcare Personalized Medicine, and elsewhere used genetic panel testing to profile more than 5,700 individuals whose self-reported race or ethnicity fell in one of three groups: white, Asian, or underrepresented minority. Their results, appearing online today in JAMA Cardiology, revealed far higher detection rates for cardiomyopathy-related variants in the white patient population.
In non-white individuals, particularly the underrepresented minority group, the team reported that inconclusive genetic test results and variants of uncertain significance were found at rates that eclipsed those in white patients.
"This clear disparity warrants further study to understand the gaps in usefulness, which may derive from a lack of clinical testing and research in underrepresented minority populations, in the hopes of improving genetic testing outcomes for cardiomyopathy in non-white groups," corresponding author Heidi Rehm, of Partners Healthcare Personalized Medicine, Brigham and Women's Hospital, Harvard Medical School, and the Broad Institute, and her colleagues wrote.
The analysis focused on 5,729 individuals from the US, Canada, and other countries who were referred for hypertrophic cardiomyopathy genetic testing at the Partners Healthcare Personalized Medicine's molecular medicine lab between the fall of 2003 and late 2017.
More than 79 percent of the participants identified as white and just over 6 percent as Asian. The remaining 842 individuals, or almost 15 percent of the participants, belonged to underrepresented minority populations and reported their ancestry or ethnicity as black, Native American, Alaskan, Hawaiian, or Pacific Islander.
The panel test successfully picked up cardiomyopathy risk factors in 29 percent of the 4,539 white individuals included in the analysis, the researchers reported. In contrast, they saw positive test results in just 155, or around 18 percent, of the underrepresented minority members. Across the 348 Asian participants profiled, the panel identified pathogenic or likely pathogenic variants in 25 percent.
In contrast, inconclusive genetic test results or variants of uncertain significance turned up in almost 40 percent of the underrepresented minorities and about 39 percent of the Asian patients, the team noted, but were found in fewer than one-quarter of the white patients.
"Our data suggest that cardiomyopathy testing has a statistically significant lower detection rate in [underrepresented minority] individuals, which is likely because of the reduction of primary data from [underrepresented minority] individuals in both the research and clinical testing settings," the authors wrote.
Further, follow up analyses on genetic testing data for hearing loss or RASopathies such as Noonan syndrome uncovered a similar discrepancy in underrepresented minorities tested for hearing loss. However, genetic testing for RASopathy found pathogenic variants at similar rates across the ancestry groups, they noted, perhaps due to the de novo nature of the causative variants involved in those conditions.
"This type of [de novo] variant typically does not require a prior evidence base to implicate the variant as likely pathogenic in a diagnostic setting," they explained, noting that "one would expect that prior efforts in research and clinical testing would not affect detection rates."
In a related JAMA Cardiology editorial, a team from the Northwestern University Feinberg School of Medicine discussed existing efforts to tally human genetic variation across populations, along with considerations for expanding such resources and selecting appropriate genetic tests for patients with cardiovascular disease.
In their own accompanying viewpoint article, Temple University researchers called inaccurate variant classification of non-European genetic tests "a major disparity in healthcare," and discussed additional factors that may affect the clinical utility and availability of genetic testing for inherited cardiac diseases in underserved populations.