Posted on August 19, 2016

Genetic Studies’ Lack of Diversity May Lead to Misdiagnoses, Researchers Say

Amy Dockser Marcus, Wall Street Journal, August 17, 2016

Doctors increasingly rely on genetic testing to help diagnose a patient’s illness or risk of getting a disease. Now a new study warns of the potential for the technology to lead to misdiagnosis.

The study looked at gene mutations previously linked to the genetic heart condition called hypertrophic cardiomyopathy and found that some patients may be at risk of being falsely diagnosed with the disease because some of the mutations are no longer considered a cause for concern.

The study was led by a team at Harvard Medical School that examined publicly available sequencing data, information in the published medical literature, and clinical records for patients tested for hypertrophic cardiomyopathy at a leading genetics lab. The researchers were particularly interested in looking at gene mutations once believed to cause hypertrophic cardiomyopathy that have since been classified as benign.


One of the researchers’ hypotheses grew from the fact that when genetic studies were first done, the numbers of people of African ancestry who were sequenced were low compared with those of European ancestry. They also knew that the misclassified gene mutations are more common in black Americans than those of different ancestries, and therefore those patients might be getting back reports that falsely led them to believe they were at higher risk to get the disease.

In studying the lab’s records, the researchers did indeed find seven people, all of African or unspecified ancestry, who got reports that said they had a mutation that might cause the disease that are now considered benign. The researchers concluded that the seven patients wouldn’t have received “false positives” on the gene tests if more blacks were sequenced and included in the databases that geneticists use to determine if a particular mutation is cause for concern.


“It is critical to revisit decades of studies forming the basis of genetic medicine today,” said Arjun K. Manrai of the Department of Biomedical Informatics at Harvard Medical School and the lead author of the study.

The paper’s authors note that a false diagnosis of a disease-causing mutation can have important consequences. People may be advised to stop playing certain sports or recommended to get a defibrillator implanted to prevent sudden cardiac death. Genetic conditions put families, not just individuals, at risk, and so does misdiagnosing such conditions. Relatives are often told to receive screening and assessments.