Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Puya Gharahkhani, Eric Jorgenson, Pirro G. Hysi, Anthony P. Khawaja, Sarah A. Pendergrass, Xikun Han, Jue‐Sheng Ong, Alex W. Hewitt, Ayellet V. Segrè, John M. Rouhana, Andrew R. Hamel, Robert P. Igo, Hélène Choquet, Ayub Qassim, Navya Shilpa Josyula, Jessica N. Cooke Bailey, Pieter W. M. Bonnemaijer, Adriana I. Iglesias, Owen M. Siggs, Terri L. Young, Véronique Vitart, Alberta A. H. J. Thiadens, Juha Karjalainen, Steffen Uebe, Ronald B. Melles, K. Saidas Nair, Robert Luben, Mark Simcoe, Nishani Amersinghe, Angela J. Cree, René Höhn, Alicia Poplawski, Li Jia Chen, Shi Song Rong, Tin Aung, Eranga N. Vithana, R. Rand Allingham, Murray H. Brilliant, Donald L. Budenz, Jessica N. Cooke Bailey, John H. Fingert, Douglas Gaasterland, Teresa Gaasterland, Jonathan L. Haines, Michael A. Hauser, Richard K. Lee, Paul R. Lichter, Yutao Liu, Syoko Moroi, Jonathan S. Myers, Margaret A. Pericak‐Vance, Anthony Realini, Doug Rhee, Julia E. Richards, Robert Ritch, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Robert N. Weinreb, Gadi Wollstein, Donald J. Zack, Shiwani Sharma, Sarah Martin, Tiger Zhou, Emmanuelle Souzeau, John E. Landers, Jude Fitzgerald, Richard Mills, Jamie E. Craig, Kathryn P. Burdon, Stuart L. Graham, Robert J. Casson, Ivan Goldberg, Andrew White, Paul R. Healey, David A. Mackey, Alex W. Hewitt, Biobank Japan project, Masaki Shiono, Kazuo Misumi, Reiji Kaieda, Hiromasa Harada, Shiro Minami, Mitsuru Emi, Naoya Emoto, Hiroyuki Daida, Katsumi Miyauchi, Akira Murakami, Satoshi Asai, Mitsuhiko Moriyama, Yasuo Takahashi, Tomoaki Fujioka, Wataru Obara, Seijiro Mori, Hideki Ito, Satoshi Nagayama, Yoshio Miki, Akihide Masumoto
Abstract
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.