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

Kathryn Burdon, Stuart Macgregor, Alex Hewitt, Shiwani Sharma, G Chidlow, Richard Mills, Patrick Danoy, R Casson, Ananth Viswanathan, Jimmy Liu, John Landers, Anjali Henders, John Wood, Emmanuelle Souzeau, April Crawford, Paul Leo, Jie Wang, E Rochtchina, Dale Nyholt, Nicholas MartinG Montgomery, Paul Mitchell, Matthew Brown, David Mackey, Jamie Craig

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)574-578
    Number of pages5
    JournalNature Genetics
    Volume43
    Issue number6
    DOIs
    Publication statusPublished - 2011

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  • Cite this

    Burdon, K., Macgregor, S., Hewitt, A., Sharma, S., Chidlow, G., Mills, R., Danoy, P., Casson, R., Viswanathan, A., Liu, J., Landers, J., Henders, A., Wood, J., Souzeau, E., Crawford, A., Leo, P., Wang, J., Rochtchina, E., Nyholt, D., ... Craig, J. (2011). Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nature Genetics, 43(6), 574-578. https://doi.org/10.1038/ng.824