Advancing Understanding of Inequities in Rare Disease Genomics.

Purpose: Advances in genomic research have led to the diagnosis of rare, early-onset diseases for thousands of individuals. Unfortunately, the benefits of advanced genetic diagnostic technology are not distributed equitably among the population, as has been seen in many other healthcare contexts. Even quantifying and describing inequities in genetic diagnostic yield is challenging due to variation in referrals to clinical genetics practices and other barriers to clinical genetic testing.

Methods: The Rare Genomes Project (RGP) at the Broad Institute of MIT and Harvard offers research genome sequencing to individuals with rare disease who remain genetically undiagnosed through direct interaction with the individual or family. This presents an opportunity for diagnosis beyond the clinical context, thus eliminating many barriers to access.

Findings: An initial goal of RGP was to equalize access to genomic sequencing by decoupling testing access from proximity to a major medical center and physician referral. However, our study participants are overwhelmingly non-disadvantaged, as evidenced by their access to specialist care and genetic testing prior to RGP enrollment, and are also predominantly white.

Implications: We therefore describe our novel initiative to diversify RGP enrollment in order to advance equity in rare disease genetic diagnosis and research. In addition to the moral imperative of medical equity, this is also critical in order to fully understand the genomic underpinnings of rare disease. We utilize a mixed methods approach to understand the priorities and values of underrepresented communities, existing disparities, and the obstacles to addressing them: all of which is necessary to promote equity in future genomic medicine initiatives.