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

Henriët Springelkamp, René Höhn, Aniket Mishra, Pirro G. Hysi, Chiea Chuen Khor, Stephanie J. Loomis, Jessica N.Cooke Bailey, Jane Gibson, Gudmar Thorleifsson, Sarah F. Janssen, Xiaoyan Luo, Wishal D. Ramdas, Eranga Vithana, Monisha E. Nongpiur, Grant W. Montgomery, Liang Xu, Jenny E. Mountain, Puya Gharahkhani, Yi Lu, Najaf AminLennart 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, 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, Geeta Menon, Blue Mountains Eye Study-GWAS groupw, Paul Mitchell, Jie Jin Wang, Elena Rochtchina, John Attia, Rodney Scott, Elizabeth G. Holliday, Paul N. Baird, Jing Xie, Michael Inouye, Ananth C. Viswanathan, Xueling Sim, Robert N. Weinreb, Paulus T.V.M. De Jong, Ben A. Oostra, André G. Uitterlinden, Albert Hofman, Sarah Ennis, Unnur Thorsteinsdottir, Kathryn P. Burdon, Wellcome Trust Case Control Consortium 2 (WTCCC2), R. Rand Allingham, Murray H. Brilliant, Donald L. Budenz, William G. Christen, John Fingert, David S. Friedman, Douglas Gaasterland, Terry Gaasterland, Jonathan L. Haines, NEIGHBORHOOD Consortium, Jae Hee Kang, Peter Kraft, Richard K. Lee, Paul R. Lichter, Yutao Liu, Sayoko E. Moroi, Margaret A. Pericak-Vance, Anthony Realini, Julia E. Richards, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Gadi Wollstein, Donald J. Zack, Kang Zhang, Ines Barroso, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Chris C.A. Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E. Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Timothy D. Spector, Alireza Mirshahi, Seang Mei Saw, Johannes R. Vingerling, Yik Ying Teo, Roger C.W. Wolfs, Hans G. Lemij, E. Shyong Tai, Nomdo M. Jansonius, Jost B. Jonas, Ching Yu Cheng, Tin Aung, Caroline C.W. Klaver, Jamie E. Craig, Stuart MacGregor, David A. MacKey, Andrew J. Lotery, Kari Stefansson, Arthur A.B. Bergen, Terri L. Young, Janey L. Wiggs, Norbert Pfeiffer, Tien Yin Wong, Louis R. Pasquale, Alex W. Hewitt, Cornelia M. Van Duijn, Christopher J. Hammond

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    Abstract

    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.

    Original languageEnglish
    Article number5883
    Number of pages7
    JournalNature Communications
    Volume5
    Issue number4883
    DOIs
    Publication statusPublished - 22 Sep 2014

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    Springelkamp, H., Höhn, R., Mishra, A., Hysi, P. G., Khor, C. C., Loomis, S. J., Bailey, J. N. C., Gibson, J., Thorleifsson, G., Janssen, S. F., Luo, X., Ramdas, W. D., Vithana, E., Nongpiur, M. E., Montgomery, G. W., Xu, L., Mountain, J. E., Gharahkhani, P., Lu, Y., ... Hammond, C. J. (2014). Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nature Communications, 5(4883), [5883]. https://doi.org/10.1038/ncomms5883