Genome-wide Association Study of Primary Angle Closure Glaucoma Quantitative Traits

Abstract

Purpose: A susceptible locus for primary angle closure glaucoma (PACG) was recently identified through the analysis of one of its quantitative traits, the anterior chamber depth. The purpose of this study is to identify the genetic determinants of other PACG-related quantitative traits, namely anterior vault (AV) and anterior chamber width (ACW), derived from anterior segment optical coherence tomography (ASOCT).

Methods: Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure ACW and AV from horizontal ASOCT scans of subjects from four population based samples namely Singapore Malay Eye Study (SiMES), Singapore Indian Eye Study (SINDI), Singapore Chinese Eye Study (SCES) and the Beijing Eye Study (BES). ACW was defined as the distance between the scleral spurs; and AV as the perpendicular distance between the corneal endothelium and the ACW. Pseudophakc or aphakic eyes were excluded. Genotyping was done using the Illumina Human 610Quad BeadChips.

Results: After quality checks, 1371 SCES, 782 SINDI, 590 SiMES and 729 BES samples remained with both genotype and ASOCT data; and these were evaluated for the association between the traits and individual SNP genotypes using linear regression, modeling for a trend-per-copy effect on the minor allele. Meta-analysis of ACW data in the four sample collections (overall N=3472) revealed several regions showing promising SNPs of borderline significance, with the most significant associations being at a locus on chromosome 1q43, an intergenic region (Pmeta = 1.16x10^-6 β meta = 0.05mm per-copy of the minor allele, Phet=0.11); and another locus (Pmeta = 2.40x10^-6 , β meta = -0.049mm per-copy of the minor allele, Phet=0.41) at a sequence variant on Chromosome 13q32.1. Meta-analysis of AV (overall N=3472) also identified several regions showing potential associations with AV, with the most significant being at a locus on chromosome 10q24.31 (Pmeta = 2.27x10^-6 β meta =-0.02mm per-copy of the minor allele, Phet=0.17).

Conclusions: We identified several potential loci influencing ACW and AV using three ethnic Asian populations. Replication in additional independent cohorts is pending to identify the true association signals for ACW and AV.