Lack of diversity in genetic studies may lead to misdiagnosis

18th August 2016

Lack of diversity in genetic studies for hypertrophic cardiomyopathy (HCM) may have led to some misdiagnoses in some ethnic communities, says a new study.

The study from Harvard Medical School published this week in The New England Journal of Medicine shows that over the last decade genetic testing may have disproportionately misdiagnosed the disease in black Americans.

The researchers found that some gene mutations thought to be disease causing in this group of people were actually harmless. They believe the problem has been caused by racially biased methods being used in early studies.

The team used gene sequencing data to identify gene mutations that had previously been classified as causing HCM, but were over-represented in the population. The disease is thought to affect 1 in 500 people, yet more than 1 in 500 people had these mutations. Looking more deeply into the data, the team found that five variants accounted for the majority of the misclassification and that those five variants were more common among African Americans.

They found that the initial studies on two variants — in the MYBPC3 and TNNI3 genes — included control samples near or below the minimum of the accepted standard needed to corroborate they were disease causing, and none of the studies implicating the variants involved people with African ancestry.

White Americans appear to have far fewer harmless mutations on several genes implicated in HCM than black Americans. Because the variants are rarer in people with European ancestry, they were falsely classified as disease causing.

For the 13 patients who received misdiagnoses, the researchers wrote that it was unclear whether the families affected were re-contacted.

The idea that genetic tests can misidentify disease-causing mutations is not entirely new. But this study is believed to be the first to trace the problem back to lack of diversity in studies.  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.

Study first author Dr Arjun Manrai, a research fellow in the Department of Biomedical Informatics at Harvard Medical School, said: "We hope our study motivates a systematic review of this issue across other genetic conditions."