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

Primary open angle glaucoma (POAG) is a leading cause of blindness world-wide. To identify new susceptibility loci, we meta-analyzed GWAS results from 8 independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significant SNPs in two Australian studies (...

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Main Authors:	Cooke Bailey, Jessica N., Loomis, Stephanie J., Kang, Jae H., Allingham, R. Rand, Gharahkhani, Puya, Khor, Chiea Chuen, Burdon, Kathryn P., Aschard, Hugues, Chasman, Daniel I., Igo, Robert P., Hysi, Pirro G., Glastonbury, Craig A., Ashley-Koch, Allison, Brilliant, Murray, Brown, Andrew A., Budenz, Donald L., Buil, Alfonso, Cheng, Ching-Yu, Choi, Hyon, Christen, William G., Curhan, Gary, De Vivo, Immaculata, Fingert, John H., Foster, Paul J., Fuchs, Charles, Gaasterland, Douglas, Gaasterland, Terry, Hewitt, Alex W., Hu, Frank, Hunter, David J., Khawaja, Anthony P., Lee, Richard K., Li, Zheng, Lichter, Paul R., Mackey, David A., McGuffin, Peter, Mitchell, Paul, Moroi, Sayoko E., Perera, Shamira A., Pepper, Keating W., Qi, Qibin, Realini, Tony, Richards, Julia E., Ridker, Paul M, Rimm, Eric, Ritch, Robert, Ritchie, Marylyn, Schuman, Joel S., Scott, William K., Singh, Kuldev, Sit, Arthur J., Song, Yeunjoo E., Tamimi, Rulla M., Topouzis, Fotis, Viswanathan, Ananth C., Verma, Shefali Setia, Vollrath, Douglas, Wang, Jie Jin, Weisschuh, Nicole, Wissinger, Bernd, Wollstein, Gadi, Wong, Tien Y., Yaspan, Brian L., Zack, Donald J., Zhang, Kang, Weinreb, Robert N., Pericak-Vance, Margaret A., Small, Kerrin, Hammond, Christopher J., Aung, Tin, Liu, Yutao, Vithana, Eranga N., MacGregor, Stuart, Craig, Jamie E., Kraft, Peter, Howell, Gareth, Hauser, Michael A., Pasquale, Louis R., Haines, Jonathan L., Wiggs, Janey L.
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731307/

id	pubmed-4731307
recordtype	oai_dc
spelling	pubmed-47313072016-07-11 Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma Cooke Bailey, Jessica N. Loomis, Stephanie J. Kang, Jae H. Allingham, R. Rand Gharahkhani, Puya Khor, Chiea Chuen Burdon, Kathryn P. Aschard, Hugues Chasman, Daniel I. Igo, Robert P. Hysi, Pirro G. Glastonbury, Craig A. Ashley-Koch, Allison Brilliant, Murray Brown, Andrew A. Budenz, Donald L. Buil, Alfonso Cheng, Ching-Yu Choi, Hyon Christen, William G. Curhan, Gary De Vivo, Immaculata Fingert, John H. Foster, Paul J. Fuchs, Charles Gaasterland, Douglas Gaasterland, Terry Hewitt, Alex W. Hu, Frank Hunter, David J. Khawaja, Anthony P. Lee, Richard K. Li, Zheng Lichter, Paul R. Mackey, David A. McGuffin, Peter Mitchell, Paul Moroi, Sayoko E. Perera, Shamira A. Pepper, Keating W. Qi, Qibin Realini, Tony Richards, Julia E. Ridker, Paul M Rimm, Eric Ritch, Robert Ritchie, Marylyn Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Song, Yeunjoo E. Tamimi, Rulla M. Topouzis, Fotis Viswanathan, Ananth C. Verma, Shefali Setia Vollrath, Douglas Wang, Jie Jin Weisschuh, Nicole Wissinger, Bernd Wollstein, Gadi Wong, Tien Y. Yaspan, Brian L. Zack, Donald J. Zhang, Kang Weinreb, Robert N. Pericak-Vance, Margaret A. Small, Kerrin Hammond, Christopher J. Aung, Tin Liu, Yutao Vithana, Eranga N. MacGregor, Stuart Craig, Jamie E. Kraft, Peter Howell, Gareth Hauser, Michael A. Pasquale, Louis R. Haines, Jonathan L. Wiggs, Janey L. Article Primary open angle glaucoma (POAG) is a leading cause of blindness world-wide. To identify new susceptibility loci, we meta-analyzed GWAS results from 8 independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significant SNPs in two Australian studies (1,252 cases and 2,592 controls), 3 European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of top SNPs identified three novel loci: rs35934224[T] within TXNRD2 (odds ratio (OR) = 0.78, P = 4.05×10−11 encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] within 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 novel targets for preventative therapies. 2016-01-11 2016-02 /pmc/articles/PMC4731307/ /pubmed/26752265 http://dx.doi.org/10.1038/ng.3482 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cooke Bailey, Jessica N. Loomis, Stephanie J. Kang, Jae H. Allingham, R. Rand Gharahkhani, Puya Khor, Chiea Chuen Burdon, Kathryn P. Aschard, Hugues Chasman, Daniel I. Igo, Robert P. Hysi, Pirro G. Glastonbury, Craig A. Ashley-Koch, Allison Brilliant, Murray Brown, Andrew A. Budenz, Donald L. Buil, Alfonso Cheng, Ching-Yu Choi, Hyon Christen, William G. Curhan, Gary De Vivo, Immaculata Fingert, John H. Foster, Paul J. Fuchs, Charles Gaasterland, Douglas Gaasterland, Terry Hewitt, Alex W. Hu, Frank Hunter, David J. Khawaja, Anthony P. Lee, Richard K. Li, Zheng Lichter, Paul R. Mackey, David A. McGuffin, Peter Mitchell, Paul Moroi, Sayoko E. Perera, Shamira A. Pepper, Keating W. Qi, Qibin Realini, Tony Richards, Julia E. Ridker, Paul M Rimm, Eric Ritch, Robert Ritchie, Marylyn Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Song, Yeunjoo E. Tamimi, Rulla M. Topouzis, Fotis Viswanathan, Ananth C. Verma, Shefali Setia Vollrath, Douglas Wang, Jie Jin Weisschuh, Nicole Wissinger, Bernd Wollstein, Gadi Wong, Tien Y. Yaspan, Brian L. Zack, Donald J. Zhang, Kang Weinreb, Robert N. Pericak-Vance, Margaret A. Small, Kerrin Hammond, Christopher J. Aung, Tin Liu, Yutao Vithana, Eranga N. MacGregor, Stuart Craig, Jamie E. Kraft, Peter Howell, Gareth Hauser, Michael A. Pasquale, Louis R. Haines, Jonathan L. Wiggs, Janey L.
spellingShingle	Cooke Bailey, Jessica N. Loomis, Stephanie J. Kang, Jae H. Allingham, R. Rand Gharahkhani, Puya Khor, Chiea Chuen Burdon, Kathryn P. Aschard, Hugues Chasman, Daniel I. Igo, Robert P. Hysi, Pirro G. Glastonbury, Craig A. Ashley-Koch, Allison Brilliant, Murray Brown, Andrew A. Budenz, Donald L. Buil, Alfonso Cheng, Ching-Yu Choi, Hyon Christen, William G. Curhan, Gary De Vivo, Immaculata Fingert, John H. Foster, Paul J. Fuchs, Charles Gaasterland, Douglas Gaasterland, Terry Hewitt, Alex W. Hu, Frank Hunter, David J. Khawaja, Anthony P. Lee, Richard K. Li, Zheng Lichter, Paul R. Mackey, David A. McGuffin, Peter Mitchell, Paul Moroi, Sayoko E. Perera, Shamira A. Pepper, Keating W. Qi, Qibin Realini, Tony Richards, Julia E. Ridker, Paul M Rimm, Eric Ritch, Robert Ritchie, Marylyn Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Song, Yeunjoo E. Tamimi, Rulla M. Topouzis, Fotis Viswanathan, Ananth C. Verma, Shefali Setia Vollrath, Douglas Wang, Jie Jin Weisschuh, Nicole Wissinger, Bernd Wollstein, Gadi Wong, Tien Y. Yaspan, Brian L. Zack, Donald J. Zhang, Kang Weinreb, Robert N. Pericak-Vance, Margaret A. Small, Kerrin Hammond, Christopher J. Aung, Tin Liu, Yutao Vithana, Eranga N. MacGregor, Stuart Craig, Jamie E. Kraft, Peter Howell, Gareth Hauser, Michael A. Pasquale, Louis R. Haines, Jonathan L. Wiggs, Janey L. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
author_facet	Cooke Bailey, Jessica N. Loomis, Stephanie J. Kang, Jae H. Allingham, R. Rand Gharahkhani, Puya Khor, Chiea Chuen Burdon, Kathryn P. Aschard, Hugues Chasman, Daniel I. Igo, Robert P. Hysi, Pirro G. Glastonbury, Craig A. Ashley-Koch, Allison Brilliant, Murray Brown, Andrew A. Budenz, Donald L. Buil, Alfonso Cheng, Ching-Yu Choi, Hyon Christen, William G. Curhan, Gary De Vivo, Immaculata Fingert, John H. Foster, Paul J. Fuchs, Charles Gaasterland, Douglas Gaasterland, Terry Hewitt, Alex W. Hu, Frank Hunter, David J. Khawaja, Anthony P. Lee, Richard K. Li, Zheng Lichter, Paul R. Mackey, David A. McGuffin, Peter Mitchell, Paul Moroi, Sayoko E. Perera, Shamira A. Pepper, Keating W. Qi, Qibin Realini, Tony Richards, Julia E. Ridker, Paul M Rimm, Eric Ritch, Robert Ritchie, Marylyn Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Song, Yeunjoo E. Tamimi, Rulla M. Topouzis, Fotis Viswanathan, Ananth C. Verma, Shefali Setia Vollrath, Douglas Wang, Jie Jin Weisschuh, Nicole Wissinger, Bernd Wollstein, Gadi Wong, Tien Y. Yaspan, Brian L. Zack, Donald J. Zhang, Kang Weinreb, Robert N. Pericak-Vance, Margaret A. Small, Kerrin Hammond, Christopher J. Aung, Tin Liu, Yutao Vithana, Eranga N. MacGregor, Stuart Craig, Jamie E. Kraft, Peter Howell, Gareth Hauser, Michael A. Pasquale, Louis R. Haines, Jonathan L. Wiggs, Janey L.
author_sort	Cooke Bailey, Jessica N.
title	Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
title_short	Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
title_full	Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
title_fullStr	Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
title_full_unstemmed	Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
title_sort	genome-wide association analysis identifies txnrd2, atxn2 and foxc1 as susceptibility loci for primary open angle glaucoma
description	Primary open angle glaucoma (POAG) is a leading cause of blindness world-wide. To identify new susceptibility loci, we meta-analyzed GWAS results from 8 independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significant SNPs in two Australian studies (1,252 cases and 2,592 controls), 3 European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of top SNPs identified three novel loci: rs35934224[T] within TXNRD2 (odds ratio (OR) = 0.78, P = 4.05×10−11 encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] within 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 novel targets for preventative therapies.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731307/
_version_	1613530035514245120

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

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