Overview
- Researchers analyzed All of Us and UK Biobank data for 167 variants across 33 IRD-linked genes in a study published in the American Journal of Human Genetics.
- They screened 317,964 All of Us participants and found 481 carriers, with only 9.4% showing an IRD diagnosis using strict ICD codes and 28.1% using broader eye-related codes.
- Validation in the UK Biobank using retinal imaging showed 16.1–27.9% of carriers had definite or possible IRD features, aligning with the U.S. estimates.
- The findings challenge assumptions of complete or near-complete penetrance for many IRD variants and indicate that carriers in the general population are far more common than previously recognized.
- Authors attribute the discrepancy to phenotypic ascertainment bias and suggest that additional genetic, epigenetic, or environmental modifiers likely determine who develops disease, with implications for genetic testing and therapy development.