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

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

doi:10.1038/ng.3079

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

Puya Gharahkhani^*, Kathryn P. Burdon, Rhys Fogarty, Shiwani Sharma, Alex W. Hewitt, Sarah Martin, Matthew H. Law, Katie Cremin, Jessica N Cooke Bailey, Stephanie J. Loomis, Louis R. Pasquale, Jonathan L. Haines, Michael A. Hauser, Ananth C. Viswanathan, Peter McGuffin, Fotis Topouzis, Paul J. Foster, Stuart L. Graham, Robert J. Casson, Mark ChehadeAndrew J. White, Tiger Zhou, Emmanuelle Souzeau, John Landers, Jude T. Fitzgerald, Sonja Klebe, Jonathan B. Ruddle, Ivan Goldberg, Paul R. Healey, Richard A. Mills, Jie Jin Wang, Grant W. Montgomery, Nicholas G. Martin, Graham Radford-Smith, David C. Whiteman, Matthew A. Brown, Janey L. Wiggs, David A. Mackey, Paul Mitchell, Stuart Macgregor, Jamie E. Craig

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

175 Citations (Scopus)

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^-19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10^-10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10^-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	6
Journal	Nature Genetics
Volume	46
Issue number	10
DOIs	https://doi.org/10.1038/ng.3079
Publication status	Published - 26 Sept 2014

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Gharahkhani, P., Burdon, K. P., Fogarty, R., Sharma, S., Hewitt, A. W., Martin, S., Law, M. H., Cremin, K., Bailey, J. N. C., Loomis, S. J., Pasquale, L. R., Haines, J. L., Hauser, M. A., Viswanathan, A. C., McGuffin, P., Topouzis, F., Foster, P. J., Graham, S. L., Casson, R. J., ... Craig, J. E. (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

@article{e0a832e78d4d48f696e6eacda841b48c,

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 × 10-19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10-10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10-10). 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.",

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

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Gharahkhani, P, Burdon, KP, Fogarty, R, Sharma, S, Hewitt, AW, Martin, S, Law, MH, Cremin, K, Bailey, JNC, Loomis, SJ, Pasquale, LR, Haines, JL, Hauser, MA, Viswanathan, AC, McGuffin, P, Topouzis, F, Foster, PJ, Graham, SL, Casson, RJ, Chehade, M, White, AJ, Zhou, T, Souzeau, E, Landers, J, Fitzgerald, JT, Klebe, S, Ruddle, JB, Goldberg, I, Healey, PR, Mills, RA, Wang, JJ, Montgomery, GW, Martin, NG, Radford-Smith, G, Whiteman, DC, Brown, MA, Wiggs, JL, Mackey, DA, Mitchell, P, Macgregor, S & Craig, JE 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 P.

AU - Fogarty, Rhys

AU - Sharma, Shiwani

AU - Hewitt, Alex W.

AU - Martin, Sarah

AU - Law, Matthew H.

AU - Cremin, Katie

AU - Bailey, Jessica N Cooke

AU - Loomis, Stephanie J.

AU - Pasquale, Louis R.

AU - Haines, Jonathan L.

AU - Hauser, Michael A.

AU - Viswanathan, Ananth C.

AU - McGuffin, Peter

AU - Topouzis, Fotis

AU - Foster, Paul J.

AU - Graham, Stuart L.

AU - Casson, Robert J.

AU - Chehade, Mark

AU - White, Andrew J.

AU - Zhou, Tiger

AU - Souzeau, Emmanuelle

AU - Landers, John

AU - Fitzgerald, Jude T.

AU - Klebe, Sonja

AU - Ruddle, Jonathan B.

AU - Goldberg, Ivan

AU - Healey, Paul R.

AU - Mills, Richard A.

AU - Wang, Jie Jin

AU - Montgomery, Grant W.

AU - Martin, Nicholas G.

AU - Radford-Smith, Graham

AU - Whiteman, David C.

AU - Brown, Matthew A.

AU - Wiggs, Janey L.

AU - Mackey, David A.

AU - Mitchell, Paul

AU - Macgregor, Stuart

AU - Craig, Jamie E.

PY - 2014/9/26

Y1 - 2014/9/26

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 × 10-19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10-10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10-10). 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 × 10-19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10-10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10-10). 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.

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

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Towards translation of glaucoma blindness genes into clinical practice: predicting Risk Of Glaucoma: RElevant SNPs with Strong Association (PROGRESSA) Study

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

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Towards translation of glaucoma blindness genes into clinical practice: predicting Risk Of Glaucoma: RElevant SNPs with Strong Association (PROGRESSA) Study

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