Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus.

Journal article

To discover quantitative trait loci for intraocular pressure, a major risk factor for glaucoma and the only modifiable one, we performed a genome-wide association study on a discovery cohort of 2175 individuals from Sydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, P(combined) = 1.10 × 10(-8)). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Authors: Blue Mountains Eye Study (BMES); Wellcome Trust Case Control Consortium 2 (WTCCC2); Strange, A; Bellenguez, C; Freeman, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Human molecular genetics
• Volume: 22
• Issue: 22
• Pages: 4653-4660
• Publication date: 2013-11-01
• DOI: 10.1093/hmg/ddt293
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Genome-Wide Association Study; Australia; Male; Adult; Wellcome Trust Case Control Consortium 2 (WTCCC2); Blue Mountains Eye Study (BMES); Prospective Studies; Cohort Studies; Female; Chromosomes, Human, Pair 7; Polymorphism, Single Nucleotide; Intraocular Pressure; Aged; Humans; Glaucoma, Open-Angle; Autoantigens; Receptors, Glucocorticoid; Genetic Variation; Alleles; Risk Factors; Middle Aged; Quantitative Trait Loci; Genetic Predisposition to Disease