Genetic testing has greatly improved physicians’ ability to detect potentially lethal heart anomalies among family members of people who suffer cardiac arrest or sudden cardiac death.
Researchers in the HMS Department of Biomedical Informatics have, however, found that over the past decade these lifesaving tools may have disproportionately misdiagnosed one cardiac condition—hypertrophic cardiomyopathy (HCM)—in Blacks. HCM, which affects one in 500 people, is an often-asymptomatic thickening of the heart muscle that can spark fatal arrhythmias in seemingly healthy young adults.
The study appeared in the August 18 issue of the New England Journal of Medicine.
Although it is recognized that genetic tests can misread benign genetic alterations as disease-causing mutations, this study may be the first one to link the problem to racially biased methodologies in early studies that defined certain common genetic variants as causes of HCM.
The analysis reveals that the misdiagnoses of HCM stemmed from clinical studies that used predominantly white populations as control groups.
Whites harbor fewer benign mutations on several genes implicated in HCM than do Blacks. The higher rate of benign alterations in the latter group can cause test results to be misread as abnormal, the researchers say.
The HMS team demonstrated that including even small numbers of Black participants in the original studies would have improved test accuracy and, consequently, helped avert some of the misdiagnoses.
The findings, the researchers say, highlight the importance of interpreting genetic test results against diverse control populations to ensure that normal variations of genetic markers common in one racial or ethnic group do not get misclassified as disease-causing in another.
“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of a larger problem that transcends a single genetic disease,” says study first author Arjun Manrai, a research fellow in the Department of Biomedical Informatics. “We hope our study motivates a systematic review of this issue across other genetic conditions.”
Aside from the emotional toll that a genetic misdiagnosis can take on individuals and families, the researchers say their findings represent a cautionary tale with a broad relevance to geneticists, clinicians and policymakers alike.
“Our study powerfully illustrates the importance of racial and ethnic diversity in research,” says Isaac Kohane, senior investigator on the study and chair of the department. “Racial and ethnic inclusiveness improves the validity and accuracy of clinical trials and, in doing so, can better guide clinical decision making and choice of optimal therapy. This is the essence of precision medicine.”
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