BioGeographical Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association with corneal thickness and disc area

Abstract

 

Purpose

 

The purpose of this study is to estimate an individual’s African admixture proportion using a novel BioGeographical Ancestry (BGA) analyses and to correlate with disease phenotype in individuals of the African Descent and Glaucoma Evaluation Study (ADAGES).

 

Methods

 

A prospective, multicenter cohort of 489 healthy, glaucoma suspect and glaucoma patients of African (AD) and European decent (ED) were included from 3 study centers. A total of 20-31 ancestry informative markers (AIMs) were selected to estimate admixture proportion1. In brief, using worldwide reference populations from five continental regions from a number of sources including the Human Genome Diversity Project, admixture proportion calls were estimated using STRUCTURE. Estimated proportion of African ancestry was correlated to central corneal thickness (CCT) and HRT based-disc area using the Spearman’s Nonparametric Test (ρ) for the total population and the Pearson correlation coefficient for the subgroups using JMP.

 

Results

 

A total of 489 subjects, consisting of 244 AD and 245 ED, successfully passed quality control measures and were included in this analysis. Among AD subjects, the median estimated African proportion was 92.0% (IQR: 75.4-97.5%). Among ED subjects, the median estimated African proportion was 0.54% (IQR: 0.39-0.98%). For the entire group, a higher African admixture proportion is significantly correlated to a smaller CCT (ρ = -0.30; p<0.0001) and to a larger disc area (ρ = 0.18; p<0.0001). While no significant associations were found within the self-described AD group, significant associations for CCT (r = -0.16; p=0.013) and borderline associations for disc area (r = 0.11; p=0.093) were seen within the ED group.

 

Conclusions

 

Increased proportion of African admixture is significantly correlated with a thinner cornea and a larger disc and separated self-described racial groups well. The lower level of association within each racial group may be due to relatively low levels of admixture within the ADAGES cohort. However, BGA does improve upon self-reported ancestry in explaining the variability of CCT within the ED group.

 

Keywords: 539 genetics • 627 optic disc • 479 cornea: clinical science