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 Martin; G Montgomery; Paul Mitchell; Matthew Brown; David Mackey; Jamie Craig

doi:10.1038/ng.824

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 language	English
Pages (from-to)	574-578
Number of pages	5
Journal	Nature Genetics
Volume	43
Issue number	6
DOIs	https://doi.org/10.1038/ng.824
Publication status	Published - Jun 2011

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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

@article{a0feb1a2b82046319c80af76004ea91c,

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

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.",

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

year = "2011",

month = jun,

doi = "10.1038/ng.824",

language = "English",

volume = "43",

pages = "574--578",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "6",

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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, Martin, N, Montgomery, G, Mitchell, P, Brown, M, Mackey, D & Craig, J 2011, 'Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1', Nature Genetics, vol. 43, no. 6, pp. 574-578. https://doi.org/10.1038/ng.824

TY - JOUR

T1 - Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

AU - Burdon, Kathryn

AU - Macgregor, Stuart

AU - Hewitt, Alex

AU - Sharma, Shiwani

AU - Chidlow, G

AU - Mills, Richard

AU - Danoy, Patrick

AU - Casson, R

AU - Viswanathan, Ananth

AU - Liu, Jimmy

AU - Landers, John

AU - Henders, Anjali

AU - Wood, John

AU - Souzeau, Emmanuelle

AU - Crawford, April

AU - Leo, Paul

AU - Wang, Jie

AU - Rochtchina, E

AU - Nyholt, Dale

AU - Martin, Nicholas

AU - Montgomery, G

AU - Mitchell, Paul

AU - Brown, Matthew

AU - Mackey, David

AU - Craig, Jamie

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.824

DO - 10.1038/ng.824

M3 - Article

SN - 1061-4036

VL - 43

SP - 574

EP - 578

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

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