Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

Abstract

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10⁻¹⁰). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

Figure 1

The 7q31 locus. (a) The pairwise correlation structure in a 600-kb interval (115.65–116.25 Mb, NCBI B36) on chromosome 7. The upper plot shows pairwise D′ for 533 common SNPs (defined as those having minor allele frequency >5%) from the Utah CEU HapMap (r22) samples. The lower plot shows the corresponding r² values. (b) Estimated sex-averaged recombination rates (saRR) in cM/Mb from the HapMap Phase II data. (c) Location of known genes in the region. (d) Schematic view of the association with POAG for all 70 markers tested in the GWAS in the region. All panels use the same horizontal scale shown in d.