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

Jessica N.Cooke Bailey; Stephanie J. Loomis; Jae H. Kang; R. Rand Allingham; Puya Gharahkhani; Chiea Chuen Khor; Kathryn P. Burdon; Hugues Aschard; Daniel I. Chasman; Robert P. Igo; Pirro G. Hysi; Craig A. Glastonbury; Allison Ashley-Koch; Murray Brilliant; Andrew A. Brown; Donald L. Budenz; Alfonso Buil; Ching Yu Cheng; Hyon Choi; William G. Christen; Gary Curhan; Immaculata De Vivo; John H. Fingert; Paul J. Foster; Charles Fuchs; Douglas Gaasterland; Terry Gaasterland; Alex W. Hewitt; Frank Hu; David J. Hunter; Anthony P. Khawaja; Richard K. Lee; Zheng Li; Paul R. Lichter; David A. Mackey; Peter McGuffin; Paul Mitchell; Sayoko E. Moroi; Shamira A. Perera; Keating W. Pepper; Qibin Qi; Tony Realini; Julia E. Richards; Paul M. Ridker; Eric Rimm; Robert Ritch; Marylyn Ritchie; Joel S. Schuman; William K. Scott; Kuldev Singh; Arthur J. Sit; Yeunjoo E. Song; Rulla M. Tamimi; Fotis Topouzis; Ananth C. Viswanathan; Shefali Setia Verma; Douglas Vollrath; Jie Jin Wang; Nicole Weisschuh; Bernd Wissinger; Gadi Wollstein; Tien Y. Wong; Brian L. Yaspan; Donald J. Zack; Kang Zhang; Robert N. Weinreb; Margaret A. Pericak-Vance; Kerrin Small; Christopher J. Hammond; Tin Aung; Yutao Liu; Eranga N. Vithana; Stuart MacGregor; Jamie E. Craig; Peter Kraft; Gareth Howell; Michael A. Hauser; Louis R. Pasquale; Jonathan L. Haines; Janey L. Wiggs

doi:10.1038/ng.3482

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

Jessica N.Cooke Bailey, Stephanie J. Loomis, Jae H. Kang, R. Rand Allingham, Puya Gharahkhani, Chiea Chuen Khor, Kathryn P. Burdon, Hugues Aschard, Daniel I. Chasman, Robert P. Igo, Pirro G. Hysi, Craig A. Glastonbury, Allison Ashley-Koch, Murray Brilliant, Andrew A. Brown, Donald L. Budenz, Alfonso Buil, Ching Yu Cheng, Hyon Choi, William G. ChristenGary Curhan, Immaculata De Vivo, John H. Fingert, Paul J. Foster, Charles Fuchs, Douglas Gaasterland, Terry Gaasterland, Alex W. Hewitt, Frank Hu, David J. Hunter, Anthony P. Khawaja, Richard K. Lee, Zheng Li, Paul R. Lichter, David A. Mackey, Peter McGuffin, Paul Mitchell, Sayoko E. Moroi, Shamira A. Perera, Keating W. Pepper, Qibin Qi, Tony Realini, Julia E. Richards, Paul M. Ridker, Eric Rimm, Robert Ritch, Marylyn Ritchie, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Yeunjoo E. Song, Rulla M. Tamimi, Fotis Topouzis, Ananth C. Viswanathan, Shefali Setia Verma, Douglas Vollrath, Jie Jin Wang, Nicole Weisschuh, Bernd Wissinger, Gadi Wollstein, Tien Y. Wong, Brian L. Yaspan, Donald J. Zack, Kang Zhang, Robert N. Weinreb, Margaret A. Pericak-Vance, Kerrin Small, Christopher J. Hammond, Tin Aung, Yutao Liu, Eranga N. Vithana, Stuart MacGregor, Jamie E. Craig, Peter Kraft, Gareth Howell, Michael A. Hauser, Louis R. Pasquale, Jonathan L. Haines, Janey L. Wiggs

School of Medicine

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

120 Scopus citations

Abstract

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 (US)
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
State	Published - Feb 1 2016

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.3482

Cite this

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., ... Wiggs, J. L. (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

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, DA, 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, Haines, JL & Wiggs, JL 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

@article{aac5b9d30fdc4aa5a0b7de9a510d4cd5,

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

abstract = "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 = "Bailey, {Jessica N.Cooke} and Loomis, {Stephanie J.} and Kang, {Jae H.} and Allingham, {R. Rand} and Puya Gharahkhani and Khor, {Chiea Chuen} and Burdon, {Kathryn P.} and Hugues Aschard and Chasman, {Daniel I.} and Igo, {Robert P.} and Hysi, {Pirro G.} and Glastonbury, {Craig A.} and Allison Ashley-Koch and Murray Brilliant and Brown, {Andrew A.} and Budenz, {Donald L.} and Alfonso Buil and Cheng, {Ching Yu} and Hyon Choi and Christen, {William G.} and Gary Curhan and {De Vivo}, Immaculata and Fingert, {John H.} and Foster, {Paul J.} and Charles Fuchs and Douglas Gaasterland and Terry Gaasterland and Hewitt, {Alex W.} and Frank Hu and Hunter, {David J.} and Khawaja, {Anthony P.} and Lee, {Richard K.} and Zheng Li and Lichter, {Paul R.} and Mackey, {David A.} and Peter McGuffin and Paul Mitchell and Moroi, {Sayoko E.} and Perera, {Shamira A.} and Pepper, {Keating W.} and Qibin Qi and Tony Realini and Richards, {Julia E.} and Ridker, {Paul M.} and Eric Rimm and Robert Ritch and Marylyn Ritchie and Schuman, {Joel S.} and Scott, {William K.} and Kuldev Singh and Sit, {Arthur J.} and Song, {Yeunjoo E.} and Tamimi, {Rulla M.} and Fotis Topouzis and Viswanathan, {Ananth C.} and Verma, {Shefali Setia} and Douglas Vollrath and Wang, {Jie Jin} and Nicole Weisschuh and Bernd Wissinger and Gadi Wollstein and Wong, {Tien Y.} and Yaspan, {Brian L.} and Zack, {Donald J.} and Kang Zhang and Weinreb, {Robert N.} and Pericak-Vance, {Margaret A.} and Kerrin Small and Hammond, {Christopher J.} and Tin Aung and Yutao Liu and Vithana, {Eranga N.} and Stuart MacGregor and Craig, {Jamie E.} and Peter Kraft and Gareth Howell and Hauser, {Michael A.} and Pasquale, {Louis R.} and Haines, {Jonathan L.} and Wiggs, {Janey L.}",

note = "Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = feb,

day = "1",

doi = "10.1038/ng.3482",

language = "English (US)",

volume = "48",

pages = "189--194",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

AU - Bailey, Jessica N.Cooke

AU - Loomis, Stephanie J.

AU - Kang, Jae H.

AU - Allingham, R. Rand

AU - Gharahkhani, Puya

AU - Khor, Chiea Chuen

AU - Burdon, Kathryn P.

AU - Aschard, Hugues

AU - Chasman, Daniel I.

AU - Igo, Robert P.

AU - Hysi, Pirro G.

AU - Glastonbury, Craig A.

AU - Ashley-Koch, Allison

AU - Brilliant, Murray

AU - Brown, Andrew A.

AU - Budenz, Donald L.

AU - Buil, Alfonso

AU - Cheng, Ching Yu

AU - Choi, Hyon

AU - Christen, William G.

AU - Curhan, Gary

AU - De Vivo, Immaculata

AU - Fingert, John H.

AU - Foster, Paul J.

AU - Fuchs, Charles

AU - Gaasterland, Douglas

AU - Gaasterland, Terry

AU - Hewitt, Alex W.

AU - Hu, Frank

AU - Hunter, David J.

AU - Khawaja, Anthony P.

AU - Lee, Richard K.

AU - Li, Zheng

AU - Lichter, Paul R.

AU - Mackey, David A.

AU - McGuffin, Peter

AU - Mitchell, Paul

AU - Moroi, Sayoko E.

AU - Perera, Shamira A.

AU - Pepper, Keating W.

AU - Qi, Qibin

AU - Realini, Tony

AU - Richards, Julia E.

AU - Ridker, Paul M.

AU - Rimm, Eric

AU - Ritch, Robert

AU - Ritchie, Marylyn

AU - Schuman, Joel S.

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur J.

AU - Song, Yeunjoo E.

AU - Tamimi, Rulla M.

AU - Topouzis, Fotis

AU - Viswanathan, Ananth C.

AU - Verma, Shefali Setia

AU - Vollrath, Douglas

AU - Wang, Jie Jin

AU - Weisschuh, Nicole

AU - Wissinger, Bernd

AU - Wollstein, Gadi

AU - Wong, Tien Y.

AU - Yaspan, Brian L.

AU - Zack, Donald J.

AU - Zhang, Kang

AU - Weinreb, Robert N.

AU - Pericak-Vance, Margaret A.

AU - Small, Kerrin

AU - Hammond, Christopher J.

AU - Aung, Tin

AU - Liu, Yutao

AU - Vithana, Eranga N.

AU - MacGregor, Stuart

AU - Craig, Jamie E.

AU - Kraft, Peter

AU - Howell, Gareth

AU - Hauser, Michael A.

AU - Pasquale, Louis R.

AU - Haines, Jonathan L.

AU - Wiggs, Janey L.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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 - 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.

UR - http://www.scopus.com/inward/record.url?scp=84956703568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956703568&partnerID=8YFLogxK

U2 - 10.1038/ng.3482

DO - 10.1038/ng.3482

M3 - Article

C2 - 26752265

AN - SCOPUS:84956703568

SN - 1061-4036

VL - 48

SP - 189

EP - 194

JO - Nature genetics

JF - Nature genetics

IS - 2

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this