The role of chromosome X in intraocular pressure variation and sex-specific effects

Abstract

PURPOSE. The purpose of this study was to identify genetic variants on chromosome X associated with intraocular pressure (IOP) and determine if they possess any sexspecific effects. METHODS. Association analyses were performed across chromosome X using 102,407 participants from the UK Biobank. Replication and validation analyses were conducted in an additional 6599 participants from the EPIC-Norfolk cohort, and an independent 331,682 participants from the UK Biobank. RESULTS. We identified three loci associated with IOP at genomewide significance (P < 5 × 10-8), located within or near the following genes: MXRA5 (rs2107482, P = 7.1 × 10-11), GPM6B (rs66819623, P = 6.9 × 10-10), NDP, and EFHC2 (rs12558081, P = 4.9 × 10-11). Alleles associated with increased IOP were also associated with increased risk for primary open-angle glaucoma in an independent sample. Finally, our results indicate that chromosome X genetics most likely do not illicit sex-specific effects on IOP. CONCLUSIONS. In this study, we report the results of genomewide levels of association of three loci on chromosome X with IOP, and provide a framework to include chromosome X in large-scale genomewide association analyses for complex phenotypes.