Key Takeaways
- Concerns have existed for years that genetic testing may perform differently across ancestry groups due to historical underrepresentation in genomic databases.
- A large study analyzing more than 73,000 patients tested with exome sequencing found no significant difference in diagnostic yield across ancestry groups.
- The findings suggest that access to testing—not diagnostic performance—is the larger barrier for many patients.
- Expanding access to genomic testing remains an important step toward equitable rare disease diagnosis.
Concerns About Representation in Genomic Databases
For years, researchers have raised an important question in genomic medicine:
If genetic testing has historically been ordered more frequently for non-Hispanic white populations, does that mean those individuals are more likely to receive a diagnosis?
The concern stems from the composition of many genomic databases. When certain populations are underrepresented in research data, interpreting genetic variants can become more challenging.
This has led some experts to question whether diagnostic rates from genomic testing might differ across ancestry groups.
What a Large Exome Study Examined
New research presented at the 2024 American Society of Human Genetics (ASHG) Annual Meeting explored this question using one of the largest datasets of its kind.
The study analyzed approximately 73,000 children with rare diseases who received exome sequencing through GeneDx. When including duo and trio testing, researchers evaluated nearly 187,000 samples in total.
The research was conducted through a collaboration between:
- GeneDx
- University of Washington
- Brotman Baty Institute for Precision Medicine
- Geisinger
- Seattle Children’s Hospital
Full study details were shared at the ASHG meeting and summarized in the announcement of the findings.¹
Diagnostic Yield Was Consistent Across Ancestry Groups
Researchers found that the diagnostic yield of exome sequencing did not differ significantly between ancestry groups.
Key findings included:
- Diagnostic rate for trio exome testing was 27.1% for underrepresented minority patients
- Diagnostic rate for non-Hispanic white patients was 27.4%
- 46% of patients evaluated were non-white
These findings suggest that ancestry alone does not significantly affect the likelihood of receiving a genetic diagnosis through exome sequencing.
Expanding Access to Genetic Testing Remains the Bigger Challenge
While diagnostic performance appeared consistent across populations, the study highlighted another issue: access to testing.
Barriers such as:
- complex diagnostic workflows
- limited access to ordering clinicians
- cost and insurance challenges
may prevent many patients from receiving genomic testing in the first place.
Improving access to genetic testing remains a critical step toward ensuring that more families can receive answers earlier in their diagnostic journey.
Clinicians interested in learning more about genomic testing approaches can explore how whole exome sequencing is used to identify the genetic causes of rare diseases.
