Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

Puya Gharahkhani; Kathryn Burdon; Rhys Fogarty; Shiwani Sharma; A W Hewitt; Sarah Martin; Matthew Law; Katie Cremin; Jessica N Cook Bailey; Stephanie Loomis; Louis Pasquale; Jonathan Haines; Michael Hauser; Ananth Viswanathan; Peter McGuffin; Fotis Topouzis; Paul J Foster; Stuart Graham; Robert Casson; Mark Chehade; Andrew J White; Tiger Zhou; Emmanuelle Souzeau; John Landers; Jude Fitzgerald; Sonja Klebe; Jonathan B Ruddle; Ivan Goldberg; Paul Healey; Wellcome Trust Case Control Consortium 2; NEIGHBORHOOD; Richard Mills; Jie Jin Wang; Grant Montgomery; Nicholas Martin; Graham Radford-Smith; David Whiteman; Matthew A Brown; Janey Wiggs; David A Mackey; Paul Mitchell; Stuart Macgregor; Jamie Craig

doi:10.1038/ng.3079

Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

Puya Gharahkhani, Kathryn Burdon, Rhys Fogarty, Shiwani Sharma, A W Hewitt, Sarah Martin, Matthew Law, Katie Cremin, Jessica N Cook Bailey, Stephanie Loomis, Louis Pasquale, Jonathan Haines, Michael Hauser, Ananth Viswanathan, Peter McGuffin, Fotis Topouzis, Paul J Foster, Stuart Graham, Robert Casson, Mark ChehadeAndrew J White, Tiger Zhou, Emmanuelle Souzeau, John Landers, Jude Fitzgerald, Sonja Klebe, Jonathan B Ruddle, Ivan Goldberg, Paul Healey, Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD , Richard Mills, Jie Jin Wang, Grant Montgomery, Nicholas Martin, Graham Radford-Smith, David Whiteman, Matthew A Brown, Janey Wiggs, David A Mackey, Paul Mitchell, Stuart Macgregor, Jamie Craig

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Abstract

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10 â '19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 â '10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 â '10). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

Original language	English
Pages (from-to)	1120-1125
Number of pages	8
Journal	Nature Genetics
Volume	46
Issue number	10
DOIs	https://doi.org/10.1038/ng.3079
Publication status	Published - 31 Aug 2014

Keywords

open-angle glaucoma
glaucoma
genome-wide association study

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Gharahkhani, P., Burdon, K., Fogarty, R., Sharma, S., Hewitt, A. W., Martin, S., Law, M., Cremin, K., Cook Bailey, J. N., Loomis, S., Pasquale, L., Haines, J., Hauser, M., Viswanathan, A., McGuffin, P., Topouzis, F., Foster, P. J., Graham, S., Casson, R., ... Craig, J. (2014). Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nature Genetics, 46(10), 1120-1125. https://doi.org/10.1038/ng.3079

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title = "Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma",

abstract = "Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10 {\^a} '19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 {\^a} '10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 {\^a} '10). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.",

keywords = "open-angle glaucoma, glaucoma, genome-wide association study",

author = "Puya Gharahkhani and Kathryn Burdon and Rhys Fogarty and Shiwani Sharma and Hewitt, {A W} and Sarah Martin and Matthew Law and Katie Cremin and {Cook Bailey}, {Jessica N} and Stephanie Loomis and Louis Pasquale and Jonathan Haines and Michael Hauser and Ananth Viswanathan and Peter McGuffin and Fotis Topouzis and Foster, {Paul J} and Stuart Graham and Robert Casson and Mark Chehade and White, {Andrew J} and Tiger Zhou and Emmanuelle Souzeau and John Landers and Jude Fitzgerald and Sonja Klebe and Ruddle, {Jonathan B} and Ivan Goldberg and Paul Healey and {Wellcome Trust Case Control Consortium 2} and NEIGHBORHOOD and Richard Mills and Wang, {Jie Jin} and Grant Montgomery and Nicholas Martin and Graham Radford-Smith and David Whiteman and Brown, {Matthew A} and Janey Wiggs and Mackey, {David A} and Paul Mitchell and Stuart Macgregor and Jamie Craig",

year = "2014",

month = aug,

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doi = "10.1038/ng.3079",

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Gharahkhani, P, Burdon, K, Fogarty, R, Sharma, S, Hewitt, AW, Martin, S, Law, M, Cremin, K, Cook Bailey, JN, Loomis, S, Pasquale, L, Haines, J, Hauser, M, Viswanathan, A, McGuffin, P, Topouzis, F, Foster, PJ, Graham, S, Casson, R, Chehade, M, White, AJ, Zhou, T, Souzeau, E , Landers, J, Fitzgerald, J, Klebe, S, Ruddle, JB, Goldberg, I, Healey, P, Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD , Mills, R, Wang, JJ, Montgomery, G, Martin, N, Radford-Smith, G, Whiteman, D, Brown, MA, Wiggs, J, Mackey, DA, Mitchell, P, Macgregor, S & Craig, J 2014, 'Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma', Nature Genetics, vol. 46, no. 10, pp. 1120-1125. https://doi.org/10.1038/ng.3079

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AU - Gharahkhani, Puya

AU - Burdon, Kathryn

AU - Fogarty, Rhys

AU - Sharma, Shiwani

AU - Hewitt, A W

AU - Martin, Sarah

AU - Law, Matthew

AU - Cremin, Katie

AU - Cook Bailey, Jessica N

AU - Loomis, Stephanie

AU - Pasquale, Louis

AU - Haines, Jonathan

AU - Hauser, Michael

AU - Viswanathan, Ananth

AU - McGuffin, Peter

AU - Topouzis, Fotis

AU - Foster, Paul J

AU - Graham, Stuart

AU - Casson, Robert

AU - Chehade, Mark

AU - White, Andrew J

AU - Zhou, Tiger

AU - Souzeau, Emmanuelle

AU - Landers, John

AU - Fitzgerald, Jude

AU - Klebe, Sonja

AU - Ruddle, Jonathan B

AU - Goldberg, Ivan

AU - Healey, Paul

AU - Wellcome Trust Case Control Consortium 2

AU - NEIGHBORHOOD

AU - Mills, Richard

AU - Wang, Jie Jin

AU - Montgomery, Grant

AU - Martin, Nicholas

AU - Radford-Smith, Graham

AU - Whiteman, David

AU - Brown, Matthew A

AU - Wiggs, Janey

AU - Mackey, David A

AU - Mitchell, Paul

AU - Macgregor, Stuart

AU - Craig, Jamie

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N2 - Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10 â '19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 â '10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 â '10). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

AB - Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10 â '19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 â '10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 â '10). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

KW - open-angle glaucoma

KW - glaucoma

KW - genome-wide association study

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Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

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