Polygenic Risk Score for Glaucoma in African Populations

Abstract

Purpose : Primary open-angle glaucoma (POAG) is the predominant type of glaucoma worldwide. Its prevalence varies greatly among ethnic groups, and is remarkably high in populations of African descent (up to 7% in West Africa). The largest genome-wide association study to date identified 127 single-nucleotide polymorphisms (SNPs), but found only few genetic factors in African populations. To evaluate the extent to which certain SNPs confer POAG risk in Africans, we calculated a polygenic risk score (PRS) in two case-control studies comprising people of African ancestry: Genetics In Glaucoma patients of African descent (GIGA) and Eyes of Africa (EoA).

Methods : We calculated a PRS based on SNPs from a meta-analysis of European and Asian populations using a fixed-effects inverse-variance weighting approach in METAL. A PRS was computed for each individual in the GIGA and EoA studies by multiplying the 1000 Genomes-imputed dosage with betas obtained from the meta-analysis. We adjusted for age, sex, and population stratification via the first 5 principal components (PCs) in our baseline model. Risk of POAG was estimated based on numerical PRS and quintile of PRS.

Results : A PRS comprising 70 loci was relatively normally distributed for controls and cases from all 6 ancestral groups: South African Black (SAB), South African Colored (SAC), Tanzanian, African-American (AA), Ghanaian (GN), and Nigerian (Figure 1). Numerical PRS and the highest quintile of PRS were associated with increased POAG odds ratios in the SAB, SAC, AA, and GN populations (Table 1). However, the addition of PRS to the baseline model only statistically significantly increased the area under the curve for the SAB and AA cohorts.

Conclusions : A PRS built from European and Asian datasets indicated that these SNPs confer POAG risk in some patients of African descent, but to a lesser extent in non-admixed populations from East and West Africa. Other SNPs may explain the substantial difference in POAG risk for African populations. Future studies on POAG in Africa should focus on identification of these SNPs.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1. Polygenic risk score (PRS) distributions and means centered by z-score for the 6 populations included in this study.

 

Table 1. Summarized statistics of a polygenic risk score (PRS) for primary open-angle glaucoma in African populations. Abbreviations:
n_tot = total number of participants
OR = Odds Ratio
CI = Confidence Interval
AUC = Area Under the Curve
PCs = Principal Components