A new study published by Ambry Genetics, examining exome sequencing outcomes across racial, ethnic, and ancestral (REA) groups reveals that disparities persist not only in the initial diagnostic yield but also in access to reanalysis.
Historically, genomic databases have been overwhelmingly populated by individuals of European descent, a bias that limits the accuracy and utility of genetic testing for people from underrepresented populations. This underrepresentation leads to a higher rate of variants of uncertain significance (VUS) and lower diagnostic yields for many non-European groups. The new research builds on this foundation, specifically exploring how REA identity influences both the results of exome sequencing and the likelihood of having data reanalyzed.
The study found that, although reanalysis improved diagnostic yields across all groups, inequities remained in who benefited from these updates. The African American and Black, Hispanic and Latino, and Asian groups experienced significantly lower rates of reanalysis compared to White patients. These gaps were primarily due to lower rates of provider-initiated reanalysis, suggesting that access to follow-up care and provider engagement are critical factors influencing equity in genetic diagnostics.
Interestingly, some groups, including Asian and Middle Eastern participants, showed higher overall rates of positive results after reanalysis, challenging prior assumptions that non-European ancestry universally correlates with lower diagnostic yield. However, the Middle Eastern group also showed significantly higher rates of uncertain results, likely reflecting continued underrepresentation in genomic reference data.
Importantly, while reclassification rates did not differ significantly across groups, the overall diagnostic yield increased by 5% after reanalysis. This finding underscores the universal benefit of reanalysis and the need to ensure equitable access for all populations.
The authors argue that current reliance on provider-initiated reanalysis perpetuates inequity. They recommend that laboratories adopt proactive, laboratory-driven reanalysis programs, which automatically reassess exome data as new information emerges. Such approaches could help reduce disparities, improve efficiency, and ensure patients receive updated results regardless of follow-up patterns or systemic barriers in care.
Ultimately, the study emphasizes that improving equity in genomic medicine requires not just diversifying reference databases, but also addressing the structural barriers embedded within the healthcare system. True equity will depend on redesigning workflows, expanding patient access to their own results, and ensuring that every individual, regardless of ancestry can benefit equally from advances in genomic science.