Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Springelkamp, Henriët; Höhn, René; Luo, Xiaoyan; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Ramdas, Wishal D.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Vithana, Eranga; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Nongpiur, Monisha E.; Droniv, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Alagurevathi; Rocketts, Michelle; Montgomery, Grant W.; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Deloukas, Panos; Brown, Matthew A.; Corvin, Aiden; Xu, Liang; Spector, Timothy D.; Mirshahi, Alireza; Saw, Seang-Mei; Vingerling, Johannes R.; Teo, Yik-Ying; Wolfs, Roger C. W.; Lemij, Hans G.; Tai, E-Shyong; Mountain, Jenny E.; Jansonius, Nomdo M.; Jonas, Jost B.; Hammond, CJ; Gharahkhani, Puya; Lu, Yi; Amin, Najaf; Mishra, Aniket; Karssen, Lennart C.; Sim, Kar-seng; van Leeuwen, Elisabeth M.; Iglesias, Adriana I.; Verhoeven, Virginie J. M.; Hauser, Michael A.; Loon, Seng-Chee; Despriet, Dominiek D. G.; Nag, Abhishek; Venturini, Cristina; Hysi, Pirro G.; Sanfilippo, Paul G.; Schillert, Arne; Kang, Jae H.; Landers, John; Jonasson, Fridbert; Cree, Angela J.; van Koolwijk, Leonieke M. E.; Rivadeneira, Fernando; Souzeau, Emmanuelle; Jonsson, Vesteinn; Khor, Chiea-Cheun; Menon, Geeta; Mitchell, Paul; Wang, Jie Jin; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth; Wong, Tien-Yin; Baird, Paul N.; Xie, Jing; Inouye, Michael; Viswanathan, Ananth; Sim, Xueling; Weinreb, Robert N.; de Jong, Paulus T. V. M.; Oostra, Ben A.; Uitterlinden, André G.; Hofman, Albert; Ennis, Sarah; Thorsteinsdottir, Unnu; Burdon, Kathryn; Allingham, R. Band; Brilliant, Murray H.; Budenz, Donald L.; Bailey, Jessica N. Cooke; Christen, William G.; Fingert, John; Friedman, David S.; Gaasterland, Douglas; Gaasterland, Terry; Gibson, Jane; Haines, Jonathan L.; Hauder, Michael A.; Kang, Jae Hee; Kraft, Peter; Lee, Richard K.; Lichter, Paul R.; Liu, Yutao; Loomis, Stephanie J.; Moroi, Sayoko E.; Pasquale, Louis R.; Thorleifsson, Gudmar; Pericak-Vance, Margaret A.; Realini, Anthony; Richards, Julia E.; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Vollrath, Douglas; Wiggs, Janey L.; Janssen, Sarah F.; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Casas, Juan P.

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

journal contribution

posted on 2025-05-10, 10:47 authored by Henriët Springelkamp, René Höhn, Xiaoyan Luo, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N. A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Wishal D. Ramdas, Ananth C. Viswanathan, Nicholas W. Wood, Chris C. A. Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Eranga Vithana, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E. Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Monisha E. Nongpiur, Serge Droniv, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Simon C. Potter, Alagurevathi Ravindrarajah, Michelle Rocketts, Grant W. Montgomery, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Panos Deloukas, Matthew A. Brown, Aiden Corvin, Liang Xu, Timothy D. Spector, Alireza Mirshahi, Seang-Mei Saw, Johannes R. Vingerling, Yik-Ying Teo, Roger C. W. Wolfs, Hans G. Lemij, E-Shyong Tai, Jenny E. Mountain, Nomdo M. Jansonius, Jost B. Jonas, CJ Hammond, Puya Gharahkhani, Yi Lu, Najaf Amin, Aniket Mishra, Lennart C. Karssen, Kar-seng Sim, Elisabeth M. van Leeuwen, Adriana I. Iglesias, Virginie J. M. Verhoeven, Michael A. Hauser, Seng-Chee Loon, Dominiek D. G. Despriet, Abhishek Nag, Cristina Venturini, Pirro G. Hysi, Paul G. Sanfilippo, Arne Schillert, Jae H. Kang, John Landers, Fridbert Jonasson, Angela J. Cree, Leonieke M. E. van Koolwijk, Fernando Rivadeneira, Emmanuelle Souzeau, Vesteinn Jonsson, Chiea-Cheun Khor, Geeta Menon, Paul Mitchell, Jie Jin Wang, Elena Rochtchina, John AttiaJohn Attia, Rodney ScottRodney Scott, Elizabeth HollidayElizabeth Holliday, Tien-Yin Wong, Paul N. Baird, Jing Xie, Michael Inouye, Ananth Viswanathan, Xueling Sim, Robert N. Weinreb, Paulus T. V. M. de Jong, Ben A. Oostra, André G. Uitterlinden, Albert Hofman, Sarah Ennis, Unnu Thorsteinsdottir, Kathryn Burdon, R. Band Allingham, Murray H. Brilliant, Donald L. Budenz, Jessica N. Cooke Bailey, William G. Christen, John Fingert, David S. Friedman, Douglas Gaasterland, Terry Gaasterland, Jane Gibson, Jonathan L. Haines, Michael A. Hauder, Jae Hee Kang, Peter Kraft, Richard K. Lee, Paul R. Lichter, Yutao Liu, Stephanie J. Loomis, Sayoko E. Moroi, Louis R. Pasquale, Gudmar Thorleifsson, Margaret A. Pericak-Vance, Anthony Realini, Julia E. Richards, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Janey L. Wiggs, Sarah F. Janssen, Gadi Wollstein, Donald J. Zack, Kang Zhang, Ines Barroso, Jenefer M. Blackwell, Elvira Bramon, Juan P. Casas

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

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Journal title

Nature Communications

Volume

5

Pagination

1-7

Publisher

Nature Publishing Group

Language

en, English

College/Research Centre

Faculty of Health and Medicine

School

School of Medicine and Public Health

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Keywords

genetics glaucoma blindness optic disc cupping

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

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