Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

作者：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, Akira Yamada, Yasuko Nishizawa, Ken Kodama, Hiromu Kutsumi, Yoshihisa Sugimoto, Yukihiro Koretsune, Hideo Kusuoka, Hideki Yanaiag, Akiko Nagai, Makoto Hirata, Yoichiro Kamatani, Kaori Muto, Koichi Matsuda, Yutaka Kiyohara, Toshiharu Ninomiya, Akiko Tamakoshi, Zentaro Yamagata, Taisei Mushiroda, Yoshinori Murakami, Koichiro Yuji, Yoichi Furukawa, Hitoshi Zembutsu, Toshihiro Tanaka, Yozo Ohnishi, Yusuke Nakamura, FinnGen study, Anu Jalanko, Jaakko Kaprio, Kati Donner, Mari Kaunisto, Nina Mars, Alexander Dada, Anastasia Shcherban, Andrea Ganna, Arto Lehistö, Elina Kilpeläinen, Georg Brein, Awaisa Ghazal, Jarmo Harju, Kalle Pärn, Pietro Della Briotta Parolo, Risto Kajanne, Susanna Lemmelä, Timo P. Sipilä, Tuomas Sipilä, Ulrike Lyhs, Vincent Llorens, Teemu Niiranen, Kati Kristiansson, Lotta Männikkö, Manuel González Jiménez, Markus Perola, Regis Wong, Terhi Kilpi, Tero Hiekkalinna, Elina Järvensivu, Essi Kaiharju, Hannele Mattsson, Markku Laukkanen, Päivi Laiho, Sini Lähteenmäki, Tuuli Sistonen, Sirpa Soini, Adam Ziemann, Anne Lehtonen, Apinya Lertratanakul, Bob Georgantas, Bridget Riley‐Gillis, Danjuma Quarless, Fedik Rahimov, Graham Heap, Howard J. Jacob, Jeffrey F. Waring, J. Wade Davis, Nizar Smaoui, Relja Popovic, Sahar Esmaeeli, Jeff Waring, Athena Matakidou, Ben Challis, David A. Close, Slavé Petrovski, Antti Karlsson, Johanna Schleutker, Kari Pulkki, Petri Virolainen, Lila Kallio, Arto Mannermaa, Sami Heikkinen, Veli‐Matti Kosma, Chia‐Yen Chen, Heiko Runz, Jimmy Liu, Paola G. Bronson, Sally John, Sanni Lahdenperä, Susan Eaton, Wei Zhou, Minna Hendolin, Outi Tuovila, Raimo Pakkanen, Joseph Maranville, Keith Usiskin, Marla Hochfeld, Robert M. Plenge, Robert Yang, Shameek Biswas, Steven M. Greenberg, Eija K. Laakkonen, Juha Kononen, Juha Paloneva, Urho M. Kujala, Teijo Kuopio, Jari A. Laukkanen, Eeva Kangasniemi, Kimmo Savinainen, Reijo Laaksonen, Mikko Arvas, Jarmo Ritari, Jukka Partanen, Kati Hyvärinen, Tiina Wahlfors, Andrew S. Peterson, Danny Oh, Diana Chang, Edmond Teng, Erich C. Strauss, Geoff Kerchner, Hao Chen, Hubert Chen, Jennifer L. Schutzman, John A. Michon, Julie Hunkapiller, Mark I. McCarthy, Natalie Bowers, Tim Lu, Tushar Bhangale, David Pulford, Dawn Waterworth, Diptee Kulkarni, Fanli Xu, Jo Betts, Jorge Esparza Gordillo, Joshua Hoffman, Kirsi Auro, Linda McCarthy, Soumitra Ghosh, Meg Ehm, Kimmo Pitkänen, Tomi P. Mäkelä, Anu Loukola, Heikki Joensuu, Juha Sinisalo, Kari K. Eklund, Lauri A. Aaltonen, Martti Färkkilâ, Olli Carpén, Paula Kauppi, Pentti Tienari, Terhi Ollila, Tiinamaija Tuomi, Tuomo J Meretoja, Anne Pitkäranta, Joni A. Turunen, Katariina Hannula‐Jouppi, Sampsa Pikkarainen, Sanna Seitsonen, Miika Koskinen, Antti Palomäki, Juha O. Rinne, Kaj Metsärinne, Klaus Elenius, Laura Pirilä, Leena Koulu, Markku Voutilainen, Markus Juonala, Sirkku Peltonen, Vesa Aaltonen, Andrey Loboda, Anna Podgornaia, Aparna Chhibber, Audrey Y. Chu, Caroline S. Fox, Dorothée Diogo, Emily Holzinger, John D. Eicher, Padhraig Gormley, Vinay Mehta, Xulong Wang, Johannes Kettunen, Katri Pylkäs, Marita Kalaoja, Minna K. Karjalainen, Reetta Hinttala, Riitta Kaarteenaho, Seppo Vainio, Tuomo Mantere, Anne M. Remes, Johanna Huhtakangas, Juhani Junttila, Kaisa Tasanen, Laura Huilaja, Marja Luodonpää, Nina Hautala, Peeter Karihtala, Saila Kauppila, Terttu Harju, Timo Blomster, Hilkka Soininen, Ilkka T. Harvima, Jussi Pihlajamäki, Kai Kaarniranta, Margit Pelkonen, Markku Laakso, Mikko Hiltunen, Mikko Kiviniemi, Oili Kaipiainen‐Seppänen, Päivi Auvinen, Reetta Kälviäinen, Valtteri Julkunen, Anders Mälarstig, Åsa K. Hedman, Catherine Marshall, Christopher D. Whelan, Heli Lehtonen, Jaakko Parkkinen, Kari Linden, Kirsi Kalpala, Melissa Miller, Nan Bing, Stefan McDonough, Xing Chen, Xinli Hu, Ying Wu, Annika Auranen, Airi Jussila, Hannele Uusitalo‐Järvinen, Hannu Kankaanranta, Hannu Uusitalo, Jukka Peltola, Mika Kähönen, Pia Isomäki, Tarja Laitinen, Teea Salmi, Anthony J. Muslin, Clarence Wang, Clément Chatelain, Ethan Xu, Franck Augé, Kathy Call, Kathy Klinger, Marika Crohns, Matthias Gossel, Kimmo Palin, Manuel A. Rivas, Harri Siirtola, Javier Gracia‐Tabuenca, Tariq Aslam, Sarah Barman, Jenny Barrett, Paul Bishop, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Valentina Cipriani, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Paul J. Foster, Marcus Fruttiger, John Gallacher, David F. Garway‐Heath, Jane Whitney Gibson, Dan Gore, Jeremy A. Guggenheim, Alison J. Hardcastle, Simon Harding, Ruth Hogg, Pearse A. Keane, Peng T. Khaw, Anthony P. Khawaja, Gerassimos Lascaratos, Andrew Lotery, Philip J. Luthert, Tom MacGillivray, Sarah Mackie, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, James P. Morgan, Zaynah Muthy, Eoin O’Sullivan, Christopher G. Owen, Praveen J. Patel, Euan Paterson, Tünde Pető, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnicka, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas G. Strouthidis, Cathie Sudlow, Caroline Thaung, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, S A Vernon, Ananth C. Viswanathan, Cathy Williams, Katie Williams, Jayne V. Woodside, Max Yates, Jennifer Yip, Yalin Zheng, Robyn J. Tapp, Denize Atan, Alex S. F. Doney, Naomi E. Allen, Thomas J. Littlejohns, Panagiotis I. Sergouniotis, Graeme C. Black, GIGA study group, Neema Kanyaro, Cyprian Ntomoka, Julius J. Massaga, Joyce K. Ikungura, Michelle Agee, Stella Aslibekyan, Robert K. Bell, Katarzyna Bryc, Sarah Clark, Sarah L. Elson, Kipper Fletez‐Brant, Pierre Fontanillas, Nicholas A. Furlotte, Pooja Gandhi, Karl Heilbron, Barry Hicks, David A. Hinds, Karen E. Huber, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Keng‐Han Lin, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Kimberly F. McManus, Joanna L. Mountain, Sahar V. Mozaffari, Priyanka Nandakumar, Elizabeth S. Noblin, Carrie A. M. Northover, Jared O’Connell, Steven J. Pitts, G. David Poznik, J. Fah Sathirapongsasuti, Anjali J. Shastri, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Robert J. Tunney, Vladimir Vacic, Amir S. Zare, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Michelle K. Lupton, Nicholas G. Martin, Adeyinka Ashaye, Olusola Olawoye, Susan Williams, Stephen Akafo, Michèle Ramsay, Kazuki Hashimoto, Yoichiro Kamatani, Masato Akiyama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae H. Kang, Chi Pui Pang, Francesca Pasutto, Paul Mitchell, Andrew Lotery, Aarno Palotie, Cornelia M. van Duijn, Jonathan L. Haines, Christopher J. Hammond, Louis R. Pasquale, Caroline C. W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Ching‐Yu Cheng, Jamie E. Craig, Stuart MacGregor, Janey L. Wiggs · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-020-20851-4 · 被引用次数：505 · 研究领域：Glaucoma and retinal disorders、Retinal Diseases and Treatments、Retinal Development and Disorders

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.