Genome-wide association study comparing patients with exfoliation syndrome and exfoliation glaucoma.

Abstract

Purpose : A high percentage of patients with exfoliation syndrome (XFS) progress to develop exfoliation glaucoma (XFG). We recently reported a genome-wide association study (GWAS) identifying CACNA1A as associated with XFS, as well as confirming strong association at LOXL1 (Nature Genetics 2015; 47:387-92). The aim of this study was to perform a genome wide, case-only comparison between XFS cases and XFG cases.

Methods : We performed age-matched, case-only genome-wide association study contrasting genome-wide genotypes of patients with XFG (N = 3000) against patients with XFS only (N = 3000). The XFG and XFS cases were enrolled from 7 countries. Meta-analysis summarizing the results across all cohorts was performed using fixed effects modeling weighted in an inverse-variance manner.

Results : Genome-wide analysis revealed a nominally significant excess of genetic markers showing suggestive evidence of association (P < 1 x 10^-5) with XFG as opposed to XFS alone. These markers map to chromosome 2p near LGALSL (OR = 0.62, P = 2.9 x 10^-6), chromosome 15q near GABRB3 (OR = 1.45, P = 4 x 10^-6), Chromosome 3q terminus (OR = 1.55, P = 6 x 10^-6), Chromosome 8q near RSPO2 (OR = 1.45, P = 4 x 10^-6), Chromosome 21q (OR = 0.68, P = 6.4 x 10^-6), and chromosome 2p near RNF144A (OR = 1.4, P = 9.8 x 10^-6). No genome-wide significant association difference was observed for XFG vs XFS.

Conclusions : Our current GWAS study did not detect genetic differences between XFS and XFG. Studies involving deployment of larger sample sizes and precise clinical phenotyping could provide with more statistical power to evaluate potential genetic differences between XFS and XFG.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.