A Population-based Genome-Wide Association Study of Anterior Chamber Width

Abstract

Purpose: : Quantitative trait loci (QTL) mapping approach can be used to identify genetic risk factors for a genetically and phenotypically complex disease such as primary angle closure glaucoma (PACG). Recently we identified a PACG susceptible locus through the analysis of a QTL for anterior chamber depth (ACD), a cardinal anatomical risk factor of PACG. The purpose of this study is to identify genetic markers responsible for the variation of another PACG related quantitative trait, anterior chamber width (ACW), derived from anterior segment optical coherence tomography (ASOCT).

Methods: : We conducted a population-based genome-wide association study (GWAS) of ACW in subjects of Chinese ethnicity from Singapore and Beijing, China. The subjects aged 40 years and over were from two well characterised population-based studies: the Singapore Chinese Eye Study (SCES) and the Beijing Eye Study (BES), respectively. Partipants underwent imaging by ASOCT (Carl Zeiss Meditec, Dublin, CA), and customized software was used to measure the ACW, defined as the distance between the scleral spurs in the horizontal (nasal-temporal) axis of ASOCT scans. Genotyping was done using the Illumina Human 610Quad BeadChips.

Results: : ASOCT measurements were available for 1573 paricipants in SCES and 915 in BES. Only the right eye of each subject were evaluated. Pseudophakc or aphakic eyes were excluded. The mean measurements of the ASOCT parameters were utilized for the GWAS. After quality checks, 1453 SCES and 831 BES samples remained with both phenotype and genotype data. Meta-analysis of ACW data in the two sample collections (overall N=2284) identified at least 5 intragenic regions showing potential associations with ACW. A locus on chromosome 7p14.3 showed the most significant association (Pmeta = 7.7 x 10^-6, βmeta = -0.0755 per-copy of the minor allele, Phet=0.31).

Conclusions: : We have identified several potential loci influencing ACW in two Chinese cohorts. Replication in additional independent cohort is pending to identify the true association signals for ACW.

Keywords: genetics • anterior segment