Diversity in Polygenic Risk of Primary Open-Angle Glaucoma

Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common glaucoma subtype, is more prevalent and severe in individuals of African ancestry. Unfortunately, this ancestral group has been historically under-represented among genetic studies of POAG. Moreover, both genetic and polygenic risk scores (GRS, PRS) that are typically based on genetic data from European-descent populations are not transferable to individuals without a majority of European ancestry. Given the aspirations of leveraging genetic information for precision medicine, GRS and PRS demonstrate clinical potential but fall short, in part due to the lack of diversity in these studies. Prioritizing diversity in the discovery of risk variants will improve the performance and utility of GRS and PRS-derived risk estimation for disease stratification, which could bring about earlier POAG intervention and treatment for a disease that often goes undetected until significant damage has occurred.

Automated summary

Glaucoma is the primary cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), which is more common and severe in individuals of African ancestry, has been historically under-represented in genetic studies. Genetic and polygenic risk scores (GRS, PRS) based on European-descent populations are not applicable to individuals without majority European ancestry. Prioritizing diversity in the discovery of risk variants will improve the performance and utility of GRS and PRS-derived risk estimation, leading to earlier intervention and treatment for POAG.