Diversity in Polygenic Risk of Primary Open-Angle Glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Public Health

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness globally.
• POAG disproportionately affects individuals of African ancestry, yet this group is under-represented in genetic research.
• Current genetic risk scores (GRS) and polygenic risk scores (PRS) are primarily based on European-ancestry data, limiting their applicability.

Purpose of the Study:

• To highlight the critical need for diversity in genetic studies of POAG.
• To underscore the limitations of current GRS and PRS in non-European populations.
• To advocate for inclusive genetic research to enhance POAG risk prediction and precision medicine.

Main Methods:

• Review of existing genetic studies on POAG.
• Analysis of the impact of population under-representation on GRS and PRS.
• Discussion of the implications for precision medicine and clinical utility.

Main Results:

• Genetic risk scores and polygenic risk scores derived from European-centric studies show reduced accuracy in other ancestral groups.
• Lack of diversity in genetic discovery cohorts leads to disparities in the clinical utility of risk prediction tools.
• Under-representation in POAG genetic studies hinders the development of effective precision medicine strategies for affected populations.

Conclusions:

• Prioritizing diversity in genetic discovery is essential for improving the performance of GRS and PRS.
• Inclusive genetic research can lead to more accurate disease stratification for earlier POAG intervention.
• Addressing diversity gaps will enhance the clinical utility of genetic information for global health equity in glaucoma treatment.