A large-scale genomic study of more than 218,000 participants in Geisinger's MyCode Community Health Initiative has revealed that rare genetic disorders (RGDs) may be more common and less clinically recognised than previously thought. Researchers found that 2.5% of participants carried high-confidence pathogenic variants linked to RGDs, yet only about one in five of those who were positive had corresponding clinical diagnoses. The findings suggest that genomic-first approaches could identify many undiagnosed cases, refine estimates of disease penetrance, and improve early diagnosis and management of RGDs.

ARTICLE

Torene, Rebecca I., et al. "A Scalable Approach for Genomic-First Rare Disorder Detection in a Healthcare-Based Population." The American Journal of Human Genetics, published online October 6, 2025. https://doi.org/10.1016/j.ajhg.2025.09.010. [not open-access]