The Role of Chromosome X in Intraocular Pressure Variation and Sex-Specific Effects

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 sex-specific 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.