Racial Disparities in Access Reduce Utility of Genetic Testing

Underrepresented minorities (URM) are less likely to receive a diagnosis from genetic testing for cardiomyopathy and are more likely to receive inconclusive testing results, compared to whites undergoing testing, according to a study published Feb. 28 in JAMA Cardiology. The authors say that these findings are the result of disparities in access to genetic testing.

"Cardiomyopathy testing has a statistically significant lower detection rate in URM individuals, which is likely because of the reduction of primary data from URM individuals in both the research and clinical testing settings," writes coauthor Latrice Landry, Ph.D., from the U.S. Food and Drug Administration in Silver Spring, Md. Furthermore, the rate of inconclusive test results is also higher in URM individuals, further undermining the utility of genetic testing in these populations and creating additional disparities for these populations beyond the fundamental lack of use of genetic testing already documented for URM individuals.

With a prevalence of 1 in every 500 individuals, cardiomyopathy is one of the most common monogenic cardiac diseases in the US population and genetic testing has become routine for the diagnosis of the condition. In the current study, the researchers analyzed molecular diagnostic testing data from 5,729 probands (male, 61.1 percent) referred for testing due to a suspected diagnosis or family history of cardiomyopathy over a 15-year period from October 2003 to December 2017.

The Laboratory for Molecular Medicine at the Partners Healthcare Personalized Medicine launched its first clinical genetic test for hypertrophic cardiomyopathy in 2003 and expanded testing to now encompass 62 genes.

The study defined URM collectively as including individuals identifying as black, Hispanic, Native American, Alaska Native, Hawaiian, and other South Pacific Islander. Those identifying as mixed race were excluded from analysis. Detection of cardiomyopathy was defined as the percentage of probands with a positive report due to identification of one or more pathogenic or likely pathogenic variants. Inconclusive findings were defined as presence of one or more variants of uncertain significance in the absence of a pathogenic or likely pathogenic variant.

The researchers found that of those tested, 79.2 percent were white, 6.1 percent were Asian individuals, and 14.7 percent were URM individuals. Positive detection occurred in significantly more white individuals versus in URM (29 percent versus 18.4 percent, respectively and 25 percent in Asian individuals). However, URM had significantly more nonconclusive test results, compared to white individuals (39.8 percent versus 24.6 percent, respectively and 39.2 percent in Asian individuals). Overall, there was a statistically significant reduction in detection rate of cardiomyopathy for URM, compared with white individuals.

"Racial/ethnic disparities in research study enrollment and the delivery of health care, favoring white individuals and racial/ethnic minorities of higher socioeconomic status, have led to differences in the development and application of the evidence base that underlies the usefulness of genetic testing," writes Landry. "This suggests greater clinical usefulness of genetic testing for cardiomyopathy in white persons in comparison with people of other racial/ethnic groups. 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 nonwhite groups."

Experts widely acknowledge that in the United States, African American individuals and most Latino/Hispanic groups are not adequately represented in genetic databases. However, there is widespread hope that ongoing efforts like the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine, the National Institutes of Health's All of Us Research Program, and the U.S. Veterans Administration's Million Veteran Project should enable better representation of the U.S. population. There is also hope that wider reimbursement will lessen disparities in access to clinical testing.

"The obvious remedy for this dearth of data is to sequence large numbers of well-phenotyped cases and controls from economically, ethnically, and racially diverse populations," writes Glenn Gerhard, M.D., in an accompanying viewpoint. "The ability of those with limited financial means to obtain fully reimbursed genetic testing for hypertrophic cardiomyopathy should significantly expand testing. Should such expansion occur, the database of genetic variants for hypertrophic cardiomyopathy and other genetic disorders in underserved populations should begin to accrue."

Takeaway: Racial disparities in access to clinical testing and participation in research have contributed to a dearth of genetic information from URM in genetic databases. Research now shows that this disparity is affecting the ability of clinical genetic testing to detect disease in URM, compared to white individuals.