# Prioritizing diversity in polygenic risk prediction of primary open-angle glaucoma

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $676,377

## Abstract

PROJECT SUMMARY: Prioritizing diversity in polygenic risk prediction of primary open-angle glaucoma
Glaucoma is the leading worldwide cause of irreversible blindness. Primary open-angle glaucoma (POAG), the
most common type of glaucoma, is more prevalent and severe in individuals of African ancestry. Unfortunately,
individuals from this ancestral group have been under-represented in genome-wide association studies
(GWAS) thus far. Furthermore, polygenic risk scores (PRS) based on GWAS data from European-descent
populations are not transferable to individuals of diverse (non-European) ancestry. Given the aspirations of
precision medicine, PRS demonstrate clinical potential but fall short, in part, due to the lack of diversity in these
studies. We hypothesize that clinically-implementable PRS can be achieved by including African and African-
descent individuals in gene discovery and PRS development.
To inform and improve precision ocular health, we will prioritize diversity in polygenic risk prediction of POAG
with three proposed aims that will yield the largest-ever meta analyses of POAG in African and African-descent
individuals and the first-ever African-ancestry focused POAG PRS. In Aim 1, we will perform meta-analyses of
47,078 samples (18,037 cases, 29,041 controls) to identify novel POAG loci in African and African-descent
populations. Given that most GWAS have been performed in mainly European and European-descent
populations, we hypothesize that undiscovered POAG risk loci will be detected by leveraging the power of
meta-analysis of case-control GWAS in African and African-descent population samples. In Aim 2, we will
meta-analyze admixture mapping results for each of our datasets to identify African ancestry-specific POAG
loci. We hypothesize that admixture mapping will identify genomic regions where African ancestry co-
segregates with POAG risk. Significant loci from Aims 1 and 2 will be fine-mapped and evaluated for selection
signatures. In Aim 3, we will build and optimize POAG PRS in African and African-descent base dataset meta-
analyses. We will then evaluate novel and published PRS for POAG classification in test datasets. We
hypothesize that ancestrally-informed POAG PRS will better predict POAG and relevant clinical outcomes in
African and African-descent populations compared to those derived from primarily European-descent data.
Meta-analysis results from Aims 1 and 2 as well as variants from our optimized PRS in Aim 3 will undergo
pathway analyses to identify biological pathways and statistical driver genes implicated in POAG risk. In the
long-term, we hope that the information gained from this project will inform a broader understanding of POAG
genetics across diverse ancestry groups and provide the foundational basis for the clinical applicability of
ancestrally-informed PRS for POAG.

## Key facts

- **NIH application ID:** 10418151
- **Project number:** 1R01EY033829-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Jessica N Cooke Bailey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $676,377
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418151

## Citation

> US National Institutes of Health, RePORTER application 10418151, Prioritizing diversity in polygenic risk prediction of primary open-angle glaucoma (1R01EY033829-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418151. Licensed CC0.

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