Genetic studies' lack of diversity may lead to misdiagnoses, researchers say

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.

Hypertrophic cardiomyopathy is best known as a cause of sudden death in young athletes. Being misdiagnosed with the condition can have major ramifications for patients and their family members.

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.

To determine if a specific gene mutation is likely to be the culprit in causing a disease, scientists need to know whether the same mutation is turning up in healthy people too—which might mean it is less worrisome—or is found only in those who actually end up getting a disease. Had there been more sequencing data from healthy black Americans, the researchers said, they would have known that the mutations weren’t likely to be the cause of the disease.