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

P. Gharahkhani; K.P. Burdon; R.D. Fogarty; S. Sharma; A.W. Hewitt; S. Martin; M.H. Law; K. Cremin; J.N.C. Bailey; S.J. Loomis; L.R. Pasquale; J.L. Haines; M.A. Hauser; A.C. Viswanathan; P.W. Mcguffin; F. Topouzis; P.J.F. Foster; S.L.D. Graham; R.J. Casson; M.J. Chehade; A.J.R. White; T. Zhou; E. Souzeau; J. Landers; J.T. Fitzgerald; S. Klebe; J.B. Ruddle; I. Goldberg; P.R. Healey; R.A.D. Mills; J. Wang; G.W. Montgomery; N.G. Martin; G.L. Radford-Smith; D.C. Whiteman; M.A. Brown; J.L. Wiggs; David Mackey; P. Mitchell; S. Macgregor; J.E. Craig

doi:10.1038/ng.3079

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

P. Gharahkhani, K.P. Burdon, R.D. Fogarty, S. Sharma, A.W. Hewitt, S. Martin, M.H. Law, K. Cremin, J.N.C. Bailey, S.J. Loomis, L.R. Pasquale, J.L. Haines, M.A. Hauser, A.C. Viswanathan, P.W. Mcguffin, F. Topouzis, P.J.F. Foster, S.L.D. Graham, R.J. Casson, M.J. ChehadeA.J.R. White, T. Zhou, E. Souzeau, J. Landers, J.T. Fitzgerald, S. Klebe, J.B. Ruddle, I. Goldberg, P.R. Healey, R.A.D. Mills, J. Wang, G.W. Montgomery, N.G. Martin, G.L. Radford-Smith, D.C. Whiteman, M.A. Brown, J.L. Wiggs, David Mackey, P. Mitchell, S. Macgregor, J.E. Craig

Centre for Ophthalmology and Visual Science (affiliated with the Lions Eye Institute)

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

172 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. © 2014 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	1120-1125
Number of pages	6
Journal	Nature Genetics
Volume	46
Issue number	10
Early online date	31 Aug 2014
DOIs	https://doi.org/10.1038/ng.3079
Publication status	Published - Oct 2014

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177327/

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Gharahkhani, P., Burdon, K. P., Fogarty, R. D., 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. W., Topouzis, F., Foster, P. J. F., Graham, S. L. D., 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{0d3e0650dd654ee093d4554901572a75,

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. {\textcopyright} 2014 Nature America, Inc. All rights reserved. ",

author = "P. Gharahkhani and K.P. Burdon and R.D. Fogarty and S. Sharma and A.W. Hewitt and S. Martin and M.H. Law and K. Cremin and J.N.C. Bailey and S.J. Loomis and L.R. Pasquale and J.L. Haines and M.A. Hauser and A.C. Viswanathan and P.W. Mcguffin and F. Topouzis and P.J.F. Foster and S.L.D. Graham and R.J. Casson and M.J. Chehade and A.J.R. White and T. Zhou and E. Souzeau and J. Landers and J.T. Fitzgerald and S. Klebe and J.B. Ruddle and I. Goldberg and P.R. Healey and R.A.D. Mills and J. Wang and G.W. Montgomery and N.G. Martin and G.L. Radford-Smith and D.C. Whiteman and M.A. Brown and J.L. Wiggs and David Mackey and P. Mitchell and S. Macgregor and J.E. Craig",

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doi = "10.1038/ng.3079",

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Gharahkhani, P, Burdon, KP, Fogarty, RD, Sharma, S, Hewitt, AW, Martin, S, Law, MH, Cremin, K, Bailey, JNC, Loomis, SJ, Pasquale, LR, Haines, JL, Hauser, MA, Viswanathan, AC, Mcguffin, PW, Topouzis, F, Foster, PJF, Graham, SLD, Casson, RJ, Chehade, MJ, White, AJR, Zhou, T, Souzeau, E, Landers, J, Fitzgerald, JT, Klebe, S, Ruddle, JB, Goldberg, I, Healey, PR, Mills, RAD, Wang, J, Montgomery, GW, Martin, NG, Radford-Smith, GL, Whiteman, DC, Brown, MA, Wiggs, JL, Mackey, D, 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

TY - JOUR

T1 - Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

AU - Gharahkhani, P.

AU - Burdon, K.P.

AU - Fogarty, R.D.

AU - Sharma, S.

AU - Hewitt, A.W.

AU - Martin, S.

AU - Law, M.H.

AU - Cremin, K.

AU - Bailey, J.N.C.

AU - Loomis, S.J.

AU - Pasquale, L.R.

AU - Haines, J.L.

AU - Hauser, M.A.

AU - Viswanathan, A.C.

AU - Mcguffin, P.W.

AU - Topouzis, F.

AU - Foster, P.J.F.

AU - Graham, S.L.D.

AU - Casson, R.J.

AU - Chehade, M.J.

AU - White, A.J.R.

AU - Zhou, T.

AU - Souzeau, E.

AU - Landers, J.

AU - Fitzgerald, J.T.

AU - Klebe, S.

AU - Ruddle, J.B.

AU - Goldberg, I.

AU - Healey, P.R.

AU - Mills, R.A.D.

AU - Wang, J.

AU - Montgomery, G.W.

AU - Martin, N.G.

AU - Radford-Smith, G.L.

AU - Whiteman, D.C.

AU - Brown, M.A.

AU - Wiggs, J.L.

AU - Mackey, David

AU - Mitchell, P.

AU - Macgregor, S.

AU - Craig, J.E.

PY - 2014/10

Y1 - 2014/10

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. © 2014 Nature America, Inc. All rights reserved.

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. © 2014 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.3079

DO - 10.1038/ng.3079

M3 - Article

SN - 1061-4036

VL - 46

SP - 1120

EP - 1125

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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