Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process
Nature Communications2014Vol. 5(1), pp. 4883–4883
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Henriët Springelkamp, René Höhn, Aniket Mishra, Pirro G. Hysi, Chiea Chuen Khor, Stephanie Loomis, Jessica N. Cooke Bailey, Jane Whitney Gibson, Guðmar Þorleifsson, Sarah F. Janssen, Xiaoyan Luo, Wishal D. Ramdas, Eranga N. Vithana, Monisha E. Nongpiur, Grant W. Montgomery, Liang Xu, Jenny Mountain, Puya Gharahkhani, Yi Lu, Najaf Amin, 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, Paul G. Sanfilippo, Arne Schillert, Jae H. Kang, John Landers, Friðbert Jónasson, Angela J. Cree, Leonieke M. E. van Koolwijk, Fernando Rivadeneira, Emmanuelle Souzeau, Vésteinn Jónsson, Geeta Menon, Blue Mountains Eye Study—GWAS group, Paul Mitchell, Jie Jin Wang, Elena Rochtchina, John Attia, Rodney J. Scott, Elizabeth G. Holliday, Tien Yin Wong, 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 Þorsteinsdóttir, Kathryn P. Burdon, R. Rand Allingham, Murray H. Brilliant, Donald L. Budenz, Jessica N. Cooke Bailey, William G. Christen, John H. Fingert, David S. Friedman, Douglas Gaasterland, Terry Gaasterland, Jonathan L. Haines, Michael A. Hauser, Jae H. Kang, Peter Kraft, Richard K. Lee, Paul R. Lichter, Yutao Liu, Stephanie Loomis, Sayoko E. Moroi, Louis R. Pasquale, Margaret A. Pericak‐Vance, Anthony Realini, Julia E. Richards, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Robert N. Weinreb, Janey L. Wiggs, Gadi Wollstein, Donald J. Zack, Kang Zhang, Peter Donnelly, Inês 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 Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Chris C. A. Spencer, Gavin Band, Céline Bellenguez, Colin L. Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah 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 Potter, Rathi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul A. Weston, Sara Widaa, Pamela Whittaker, Inês Barroso, Panos Deloukas, Jenefer M. Blackwell, Jenefer M. Blackwell, Matthew A. Brown, Aiden Corvin, Chris C. A. Spencer, Timothy D. Spector, Alireza Mirshahi, Seang‐Mei Saw, Johannes R. Vingerling, Yik-Ying Teo, Jonathan L. Haines, Roger C. W. Wolfs, Hans G. Lemij, E Shyong Tai, Nomdo M. Jansonius, Jost B. Jonas, Ching‐Yu Cheng, Tin Aung, Ananth C. Viswanathan, Caroline C. W. Klaver, Jamie E. Craig, Stuart MacGregor, David A. Mackey, Andrew Lotery, Kāri Stefánsson, Arthur A. 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
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.
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