Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process
Authors: Springelkamp Henriët. , Höhn René , Mishra Aniket , Hysi Pirro G. , Khor Chiea-Chuen , Loomis Stephanie J. , Bailey Jessica N. Cooke , Gibson Jane , Thorleifsson Gudmar , Janssen Sarah F. , Luo Xiaoyan , Ramdas Wishal D. , Vithana Eranga , Nongpiur Monisha E. , Montgomery Grant W. , Xu Liang , Mountain Jenny E. , Gharahkhani Puya , Lu Yi , Amin Najaf , 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 , 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 , Menon Geeta ,   Blue Mountains Eye Study—GWAS group, Mitchell Paul , Wang Jie Jin , Rochtchina Elena , Attia John , Scott Rodney , Holliday Elizabeth G. , 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 Unnur , Burdon Kathryn P. ,   NEIGHBORHOOD Consortium, Allingham R. Rand , Brilliant Murray H. , Budenz Donald L. , Cooke Bailey Jessica N. , Christen William G. , Fingert John , Friedman David S. , Gaasterland Douglas , Gaasterland Terry , Haines Jonathan L. , Hauser Michael A. , Kang Jae Hee , Kraft Peter , Lee Richard K. , Lichter Paul R. , Liu Yutao , Loomis Stephanie J. , Moroi Sayoko E. , Pasquale Louis R. , Pericak-Vance Margaret A. , Realini Anthony , Richards Julia E. , Schuman Joel S. , Scott William K. , Singh Kuldev , Sit Arthur J. , Vollrath Douglas , Weinreb Robert N. , Wiggs Janey L. , Wollstein Gadi , Zack Donald J. , Zhang Kang ,   Wellcome Trust Case Control Consortium 2 (WTCCC2), Donnelly Peter , Barroso Ines , Blackwell Jenefer M. , Bramon Elvira , Brown Matthew A. , Casas Juan P. , Corvin Aiden , Deloukas Panos , Duncanson Audrey , Jankowski Janusz , Markus Hugh S. , Mathew Christopher G. , Palmer Colin N. A. , Plomin Robert , Rautanen Anna , Sawcer Stephen J. , Trembath Richard C. , Viswanathan Ananth C. , Wood Nicholas W. , Spencer Chris C. A. , Band Gavin , Bellenguez Céline , Freeman Colin , Hellenthal Garrett , Giannoulatou Eleni , Pirinen Matti , Pearson Richard , Strange Amy , Su Zhan , Vukcevic Damjan , Donnelly Peter , Langford Cordelia , Hunt Sarah E. , Edkins Sarah , Gwilliam Rhian , Blackburn Hannah , Bumpstead Suzannah J. , Dronov Serge , Gillman Matthew , Gray Emma , Hammond Naomi , Jayakumar Alagurevathi , McCann Owen T. , Liddle Jennifer , Potter Simon C. , Ravindrarajah Radhi , Ricketts Michelle , Waller Matthew , Weston Paul , Widaa Sara , Whittaker Pamela , Barroso Ines , Deloukas Panos , Mathew Christopher G. , Blackwell Jenefer M. , Brown Matthew A. , Corvin Aiden , Spencer Chris C. A. , Spector Timothy D. , Mirshahi Alireza , Saw Seang-Mei , Vingerling Johannes R. , Teo Yik-Ying , Haines Jonathan L. , Wolfs Roger C. W. , Lemij Hans G. , Tai E-Shyong , Jansonius Nomdo M. , Jonas Jost B. , Cheng Ching-Yu , Aung Tin , Viswanathan Ananth C. , Klaver Caroline C. W. , Craig Jamie E. , Macgregor Stuart , Mackey David A. , Lotery Andrew J. , Stefansson Kari , Bergen Arthur A. B. , Young Terri L. , Wiggs Janey L. , Pfeiffer Norbert , Wong Tien-Yin , Pasquale Louis R. , Hewitt Alex W. , van Duijn Cornelia M. , Hammond Christopher J. 
Published: September 2014

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.