Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

J.N.C. Bailey; S.J. Loomis; J.H. Kang; R.R. Allingham; P. Gharahkhani; C.C. Khor; K.P. Burdon; H. Aschard; D.I. Chasman; R.P. Igo; P.G. Hysi; C.A. Glastonbury; A. Ashley-Koch; M. Brilliant; A.A. Brown; D.L. Budenz; A. Buil; C.Y. Cheng; H. Choi; W.G. Christen; G. Curhan; I. De Vivo; J.H. Fingert; P.J. Foster; C. Fuchs; D. Gaasterland; T. Gaasterland; A.W. Hewitt; F. Hu; D.J. Hunter; A.P. Khawaja; R.K. Lee; Z. Li; P.R. Lichter; David Mackey; P. Mcguffin; P. Mitchell; S.E. Moroi; S.A. Perera; K.W. Pepper; Q. Qi; T. Realini; J.E. Richards; P.M. Ridker; E. Rimm; R. Ritch; M. Ritchie; J.S. Schuman; W.K. Scott; K. Singh; A.J. Sit; Y.E. Song; R.M. Tamimi; F. Topouzis; A.C. Viswanathan; S.S. Verma; D. Vollrath; J.J. Wang; N. Weisschuh; B. Wissinger; G. Wollstein; T.Y. Wong; B.L. Yaspan; D.J. Zack; K. Zhang; R.N. Weinreb; M.A. Pericak-Vance; K. Small; C.J. Hammond; T. Aung; Y. Liu; E.N. Vithana; S. Macgregor; J.E. Craig; P. Kraft; G. Howell; M.A. Hauser; L.R. Pasquale

doi:10.1038/ng.3482

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

J.N.C. Bailey, S.J. Loomis, J.H. Kang, R.R. Allingham, P. Gharahkhani, C.C. Khor, K.P. Burdon, H. Aschard, D.I. Chasman, R.P. Igo, P.G. Hysi, C.A. Glastonbury, A. Ashley-Koch, M. Brilliant, A.A. Brown, D.L. Budenz, A. Buil, C.Y. Cheng, H. Choi, W.G. ChristenG. Curhan, I. De Vivo, J.H. Fingert, P.J. Foster, C. Fuchs, D. Gaasterland, T. Gaasterland, A.W. Hewitt, F. Hu, D.J. Hunter, A.P. Khawaja, R.K. Lee, Z. Li, P.R. Lichter, David Mackey, P. Mcguffin, P. Mitchell, S.E. Moroi, S.A. Perera, K.W. Pepper, Q. Qi, T. Realini, J.E. Richards, P.M. Ridker, E. Rimm, R. Ritch, M. Ritchie, J.S. Schuman, W.K. Scott, K. Singh, A.J. Sit, Y.E. Song, R.M. Tamimi, F. Topouzis, A.C. Viswanathan, S.S. Verma, D. Vollrath, J.J. Wang, N. Weisschuh, B. Wissinger, G. Wollstein, T.Y. Wong, B.L. Yaspan, D.J. Zack, K. Zhang, R.N. Weinreb, M.A. Pericak-Vance, K. Small, C.J. Hammond, T. Aung, Y. Liu, E.N. Vithana, S. Macgregor, J.E. Craig, P. Kraft, G. Howell, M.A. Hauser, L.R. Pasquale

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

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Abstract

© 2016 Nature America, Inc. Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Original language	English
Pages (from-to)	189-194
Number of pages	6
Journal	Nature Genetics
Volume	48
Issue number	2
DOIs	https://doi.org/10.1038/ng.3482
Publication status	Published - 1 Feb 2016

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10.1038/ng.3482

Cooke Bailey, J., Loomis, S., Kang, J., Allingham, R., Gharahkhani, P., Khor, C., Burdon, K., et al., 2016 Genome-wide associationAccepted author manuscript, 493 KBLicence: CC BY-NC-SA

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Bailey, J. N. C., Loomis, S. J., Kang, J. H., Allingham, R. R., Gharahkhani, P., Khor, C. C., Burdon, K. P., Aschard, H., Chasman, D. I., Igo, R. P., Hysi, P. G., Glastonbury, C. A., Ashley-Koch, A., Brilliant, M., Brown, A. A., Budenz, D. L., Buil, A., Cheng, C. Y., Choi, H., ... Pasquale, L. R. (2016). Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nature Genetics, 48(2), 189-194. https://doi.org/10.1038/ng.3482

@article{b2085b41a8be48b3a9fc1b9c919863a9,

title = "Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma",

abstract = "{\textcopyright} 2016 Nature America, Inc. Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.",

author = "J.N.C. Bailey and S.J. Loomis and J.H. Kang and R.R. Allingham and P. Gharahkhani and C.C. Khor and K.P. Burdon and H. Aschard and D.I. Chasman and R.P. Igo and P.G. Hysi and C.A. Glastonbury and A. Ashley-Koch and M. Brilliant and A.A. Brown and D.L. Budenz and A. Buil and C.Y. Cheng and H. Choi and W.G. Christen and G. Curhan and {De Vivo}, I. and J.H. Fingert and P.J. Foster and C. Fuchs and D. Gaasterland and T. Gaasterland and A.W. Hewitt and F. Hu and D.J. Hunter and A.P. Khawaja and R.K. Lee and Z. Li and P.R. Lichter and David Mackey and P. Mcguffin and P. Mitchell and S.E. Moroi and S.A. Perera and K.W. Pepper and Q. Qi and T. Realini and J.E. Richards and P.M. Ridker and E. Rimm and R. Ritch and M. Ritchie and J.S. Schuman and W.K. Scott and K. Singh and A.J. Sit and Y.E. Song and R.M. Tamimi and F. Topouzis and A.C. Viswanathan and S.S. Verma and D. Vollrath and J.J. Wang and N. Weisschuh and B. Wissinger and G. Wollstein and T.Y. Wong and B.L. Yaspan and D.J. Zack and K. Zhang and R.N. Weinreb and M.A. Pericak-Vance and K. Small and C.J. Hammond and T. Aung and Y. Liu and E.N. Vithana and S. Macgregor and J.E. Craig and P. Kraft and G. Howell and M.A. Hauser and L.R. Pasquale",

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Bailey, JNC, Loomis, SJ, Kang, JH, Allingham, RR, Gharahkhani, P, Khor, CC, Burdon, KP, Aschard, H, Chasman, DI, Igo, RP, Hysi, PG, Glastonbury, CA, Ashley-Koch, A, Brilliant, M, Brown, AA, Budenz, DL, Buil, A, Cheng, CY, Choi, H, Christen, WG, Curhan, G, De Vivo, I, Fingert, JH, Foster, PJ, Fuchs, C, Gaasterland, D, Gaasterland, T, Hewitt, AW, Hu, F, Hunter, DJ, Khawaja, AP, Lee, RK, Li, Z, Lichter, PR, Mackey, D, Mcguffin, P, Mitchell, P, Moroi, SE, Perera, SA, Pepper, KW, Qi, Q, Realini, T, Richards, JE, Ridker, PM, Rimm, E, Ritch, R, Ritchie, M, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Song, YE, Tamimi, RM, Topouzis, F, Viswanathan, AC, Verma, SS, Vollrath, D, Wang, JJ, Weisschuh, N, Wissinger, B, Wollstein, G, Wong, TY, Yaspan, BL, Zack, DJ, Zhang, K, Weinreb, RN, Pericak-Vance, MA, Small, K, Hammond, CJ, Aung, T, Liu, Y, Vithana, EN, Macgregor, S, Craig, JE, Kraft, P, Howell, G, Hauser, MA & Pasquale, LR 2016, 'Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma', Nature Genetics, vol. 48, no. 2, pp. 189-194. https://doi.org/10.1038/ng.3482

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AU - Loomis, S.J.

AU - Kang, J.H.

AU - Allingham, R.R.

AU - Gharahkhani, P.

AU - Khor, C.C.

AU - Burdon, K.P.

AU - Aschard, H.

AU - Chasman, D.I.

AU - Igo, R.P.

AU - Hysi, P.G.

AU - Glastonbury, C.A.

AU - Ashley-Koch, A.

AU - Brilliant, M.

AU - Brown, A.A.

AU - Budenz, D.L.

AU - Buil, A.

AU - Cheng, C.Y.

AU - Choi, H.

AU - Christen, W.G.

AU - Curhan, G.

AU - De Vivo, I.

AU - Fingert, J.H.

AU - Foster, P.J.

AU - Fuchs, C.

AU - Gaasterland, D.

AU - Gaasterland, T.

AU - Hewitt, A.W.

AU - Hu, F.

AU - Hunter, D.J.

AU - Khawaja, A.P.

AU - Lee, R.K.

AU - Li, Z.

AU - Lichter, P.R.

AU - Mackey, David

AU - Mcguffin, P.

AU - Mitchell, P.

AU - Moroi, S.E.

AU - Perera, S.A.

AU - Pepper, K.W.

AU - Qi, Q.

AU - Realini, T.

AU - Richards, J.E.

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AU - Singh, K.

AU - Sit, A.J.

AU - Song, Y.E.

AU - Tamimi, R.M.

AU - Topouzis, F.

AU - Viswanathan, A.C.

AU - Verma, S.S.

AU - Vollrath, D.

AU - Wang, J.J.

AU - Weisschuh, N.

AU - Wissinger, B.

AU - Wollstein, G.

AU - Wong, T.Y.

AU - Yaspan, B.L.

AU - Zack, D.J.

AU - Zhang, K.

AU - Weinreb, R.N.

AU - Pericak-Vance, M.A.

AU - Small, K.

AU - Hammond, C.J.

AU - Aung, T.

AU - Liu, Y.

AU - Vithana, E.N.

AU - Macgregor, S.

AU - Craig, J.E.

AU - Kraft, P.

AU - Howell, G.

AU - Hauser, M.A.

AU - Pasquale, L.R.

PY - 2016/2/1

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N2 - © 2016 Nature America, Inc. Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

AB - © 2016 Nature America, Inc. Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

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ER -

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

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Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

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Genes for juvenile-onset myopia

Translation of Genetic Eye Research Integrating Education, Counselling & Testing with Gene Discovery & Gene Based Therapies for Eye Disease

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