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Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
journal contribution
posted on 2023-05-17, 10:20 authored by Kathryn BurdonKathryn Burdon, Macgregor, S, Alexander HewittAlexander Hewitt, Sharma, S, Chidlow, G, Mills, RA, Danoy, P, Casson, R, Viswanathan, AC, Liu, JZ, Landers, J, Henders, AK, Wood, J, Souzeau, E, Crawford, A, Leo, P, Wang, JJ, Rochtchina, E, Nyholt, DR, Martin, NG, Montgomery, GW, Mitchell, P, Brown, MA, David MackeyDavid Mackey, Craig, JEWe 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 x 10−10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 x 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 x 10−14, OR = 1.51, 95% CI 1.35–1.68; rs4977756 combined P = 1.35 x 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.
History
Publication title
Nature GeneticsVolume
43Issue
6Pagination
574-578ISSN
1061-4036Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
345 Park Ave South, New York, USA, Ny, 10010-1707Rights statement
© 2011 Nature Publishing GroupRepository Status
- Restricted