Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

Burdon, K. P., MacGregor, S., Hewitt, A. W., Sharma, S., Chidlow, G., Mills, R. A., Danoy, P., Casson, R., Viswanathan, A. C., Liu, J. Z., Landers, J., Henders, A. K., Wood, J., Souzeau, E., Crawford, A., Leo, P., Wang, J. J., Rochtchina, E., Nyholt, D.R., Martin, N.G., Montgomery, G.W., Mitchell, P., Brown, M.A., MacKey, D.A., & Craig, J. E. (2011) Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nature Genetics, 43(6), pp. 574-578.

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We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.

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ID Code: 89379
Item Type: Journal Article
Refereed: Yes
Keywords: cyclin dependent kinase inhibitor 2A, cyclin dependent kinase inhibitor 2B, membrane protein, protein TMCO1, unclassified drug, 3' untranslated region, adult, aged, animal experiment, animal model, article, cohort analysis, controlled study, disease severity, female, gene expression, gene frequency, gene identification, gene linkage disequilibrium, gene locus, gene replication, genetic association, genetic susceptibility, genetic variability, genome analysis, genotype, haplotype, human, human tissue, male, nonhuman, nucleotide sequence, open angle glaucoma, priority journal, rat, retina, reverse transcription polymerase chain reaction, visual field defect, Aged, 80 and over, Animals, Cyclin-Dependent Kinase Inhibitor p15, Cytoskeletal Proteins, Eye Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, Glycoproteins, Humans, Polymorphism, Single Nucleotide, Rats, Rattus
DOI: 10.1038/ng.824
ISSN: 1061-4036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 Nature America
Deposited On: 22 Oct 2015 02:16
Last Modified: 26 Feb 2016 02:26

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