Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Authors: Gharahkhani Puya , Jorgenson Eric , Hysi Pirro , Khawaja Anthony P. , Pendergrass Sarah , Han Xikun , Ong Jue Sheng , Hewitt Alex W. , Segrè Ayellet V. , Rouhana John M. , Hamel Andrew R. , Igo Robert P. , Choquet Helene , Qassim Ayub , Josyula Navya S. , Cooke Bailey Jessica N. , Bonnemaijer Pieter W. M. , Iglesias Adriana , Siggs Owen M. , Young Terri L. , Vitart Veronique , Thiadens Alberta A. H. J. , Karjalainen Juha , Uebe Steffen , Melles Ronald B. , Nair K. Saidas , Luben Robert , Simcoe Mark , Amersinghe Nishani , Cree Angela J. , Hohn Rene , Poplawski Alicia , Chen Li Jia , Rong Shi-Song , Aung Tin , Vithana Eranga Nishanthie ,   NEIGHBORHOOD consortium, Allingham R. Rand , Brilliant Murray , Budenz Donald L. , Bailey Jessica N. Cooke , Fingert John H. , Gaasterland Douglas , Gaasterland Teresa , Haines Jonathan L. , Hauser Michael , Lee Richard K. , Lichter Paul R. , Liu Yutao , Moroi Syoko , Myers Jonathan , Pericak-Vance Margaret , Realini Anthony , Rhee Doug , Richards Julia E. , Ritch Robert , Schuman Joel S. , Scott William K. , Singh Kuldev , Sit Arthur J. , Vollrath Douglas , Weinreb Robert N. , Wollstein Gadi , Zack Donald J. ,   ANZRAG consortium, Sharma Shiwani , Martin Sarah , Zhou Tiger , Souzeau Emmanuelle , Landers John , Fitzgerald Jude T. , Mills Richard A. , Craig Jamie , Burdon Kathryn , Graham Stuart L. , Casson Robert J. , Goldberg Ivan , White Andrew J. , Healey Paul R. , Mackey David A. , Hewitt Alex W. ,   Biobank Japan project, Shiono Masaki , Misumi Kazuo , Kaieda Reiji , Harada Hiromasa , Minami Shiro , Emi Mitsuru , Emoto Naoya , Daida Hiroyuki , Miyauchi Katsumi , Murakami Akira , Asai Satoshi , Moriyama Mitsuhiko , Takahashi Yasuo , Fujioka Tomoaki , Obara Wataru , Mori Seijiro , Ito Hideki , Nagayama Satoshi , Miki Yoshio , Masumoto Akihide , Yamada Akira , Nishizawa Yasuko , Kodama Ken , Kutsumi Hiromu , Sugimoto Yoshihisa , Koretsune Yukihiro , Kusuoka Hideo , Yanaiag Hideki , Nagai Akiko , Hirata Makoto , Kamatani Yoichiro , Muto Kaori , Matsuda Koichi , Kiyohara Yutaka , Ninomiya Toshiharu , Tamakoshi Akiko , Yamagata Zentaro , Mushiroda Taisei , Murakami Yoshinori , Yuji Koichiro , Furukawa Yoichi , Zembutsu Hitoshi , Tanaka Toshihiro , Ohnishi Yozo , Nakamura Yusuke ,   FinnGen study, Jalanko Anu , Kaprio Jaakko , Donner Kati , Kaunisto Mari , Mars Nina , Dada Alexander , Shcherban Anastasia , Ganna Andrea , Lehisto Arto , Kilpeläinen Elina , Brein Georg , Awaisa Ghazal , Harju Jarmo , Pärn Kalle , Della Briotta Parolo Pietro , Kajanne Risto , Lemmelä Susanna , Sipilä Timo P. , Sipilä Tuomas , Lyhs Ulrike , Llorens Vincent , Niiranen Teemu , Kristiansson Kati , Männikkö Lotta , Jiménez Manuel González , Perola Markus , Wong Regis , Kilpi Terhi , Hiekkalinna Tero , Järvensivu Elina , Kaiharju Essi , Mattsson Hannele , Laukkanen Markku , Laiho Päivi , Lähteenmäki Sini , Sistonen Tuuli , Soini Sirpa , Ziemann Adam , Lehtonen Anne , Lertratanakul Apinya , Georgantas Bob , Riley-Gillis Bridget , Quarless Danjuma , Rahimov Fedik , Heap Graham , Jacob Howard , Waring Jeffrey , Davis Justin Wade , Smaoui Nizar , Popovic Relja , Esmaeeli Sahar , Waring Jeff , Matakidou Athena , Challis Ben , Close David , Petrovski Slavé , Karlsson Antti , Schleutker Johanna , Pulkki Kari , Virolainen Petri , Kallio Lila , Mannermaa Arto , Heikkinen Sami , Kosma Veli-Matti , Chen Chia-Yen , Runz Heiko , Liu Jimmy , Bronson Paola , John Sally , Lahdenperä Sanni , Eaton Susan , Zhou Wei , Hendolin Minna , Tuovila Outi , Pakkanen Raimo , Maranville Joseph , Usiskin Keith , Hochfeld Marla , Plenge Robert , Yang Robert , Biswas Shameek , Greenberg Steven , Laakkonen Eija , Kononen Juha , Paloneva Juha , Kujala Urho , Kuopio Teijo , Laukkanen Jari , Kangasniemi Eeva , Savinainen Kimmo , Laaksonen Reijo , Arvas Mikko , Ritari Jarmo , Partanen Jukka , Hyvärinen Kati , Wahlfors Tiina , Peterson Andrew , Oh Danny , Chang Diana , Teng Edmond , Strauss Erich , Kerchner Geoff , Chen Hao , Chen Hubert , Schutzman Jennifer , Michon John , Hunkapiller Julie , McCarthy Mark , Bowers Natalie , Lu Tim , Bhangale Tushar , Pulford David , Waterworth Dawn , Kulkarni Diptee , Xu Fanli , Betts Jo , Gordillo Jorge Esparza , Hoffman Joshua , Auro Kirsi , McCarthy Linda , Ghosh Soumitra , Ehm Meg , Pitkänen Kimmo , Mäkelä Tomi , Loukola Anu , Joensuu Heikki , Sinisalo Juha , Eklund Kari , Aaltonen Lauri , Färkkilä Martti , Carpen Olli , Kauppi Paula , Tienari Pentti , Ollila Terhi , Tuomi Tiinamaija , Meretoja Tuomo , Pitkäranta Anne , Turunen Joni , Hannula-Jouppi Katariina , Pikkarainen Sampsa , Seitsonen Sanna , Koskinen Miika , Palomäki Antti , Rinne Juha , Metsärinne Kaj , Elenius Klaus , Pirilä Laura , Koulu Leena , Voutilainen Markku , Juonala Markus , Peltonen Sirkku , Aaltonen Vesa , Loboda Andrey , Podgornaia Anna , Chhibber Aparna , Chu Audrey , Fox Caroline , Diogo Dorothee , Holzinger Emily , Eicher John , Gormley Padhraig , Mehta Vinay , Wang Xulong , Kettunen Johannes , Pylkäs Katri , Kalaoja Marita , Karjalainen Minna , Hinttala Reetta , Kaarteenaho Riitta , Vainio Seppo , Mantere Tuomo , Remes Anne , Huhtakangas Johanna , Junttila Juhani , Tasanen Kaisa , Huilaja Laura , Luodonpää Marja , Hautala Nina , Karihtala Peeter , Kauppila Saila , Harju Terttu , Blomster Timo , Soininen Hilkka , Harvima Ilkka , Pihlajamäki Jussi , Kaarniranta Kai , Pelkonen Margit , Laakso Markku , Hiltunen Mikko , Kiviniemi Mikko , Kaipiainen-Seppänen Oili , Auvinen Päivi , Kälviäinen Reetta , Julkunen Valtteri , Malarstig Anders , Hedman Åsa , Marshall Catherine , Whelan Christopher , Lehtonen Heli , Parkkinen Jaakko , Linden Kari , Kalpala Kirsi , Miller Melissa , Bing Nan , McDonough Stefan , Chen Xing , Hu Xinli , Wu Ying , Auranen Annika , Jussila Airi , Uusitalo-Järvinen Hannele , Kankaanranta Hannu , Uusitalo Hannu , Peltola Jukka , Kähönen Mika , Isomäki Pia , Laitinen Tarja , Salmi Teea , Muslin Anthony , Wang Clarence , Chatelain Clement , Xu Ethan , Auge Franck , Call Kathy , Klinger Kathy , Crohns Marika , Gossel Matthias , Palin Kimmo , Rivas Manuel , Siirtola Harri , Tabuenca Javier Gracia ,   UK Biobank Eye and Vision Consortium, Aslam Tariq , Barman Sarah , Barrett Jenny , Bishop Paul , Bunce Catey , Carare Roxana , Chakravarthy Usha , Chan Michelle , Cipriani Valentina , Day Alexander , Desai Parul , Dhillon Bal , Dick Andrew , Egan Cathy , Ennis Sarah , Foster Paul , Fruttiger Marcus , Gallacher John , Garway-Heath David , Gibson Jane , Gore Dan , Guggenheim Jeremy , Hardcastle Alison , Harding Simon , Hogg Ruth , Keane Pearse A. , Khaw Peng T. , Khawaja Anthony , Lascaratos Gerassimos , Lotery Andrew J. , Luthert Phil , Macgillivray Tom , Mackie Sarah , Mcguinness Bernadette , Mckay Gareth , Mckibbin Martin , Mitry Danny , Moore Tony , Morgan James , Muthy Zaynah , O’Sullivan Eoin , Owen Chris , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Rahi Jugnoo , Rudnicka Alicja , Self Jay , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Thaung Caroline , Thomas Dhanes , Trucco Emanuele , Tufail Adnan , Vernon Stephen , Viswanathan Ananth , Williams Cathy , Williams Katie , Woodside Jayne , Yates Max , Yip Jennifer , Zheng Yalin , Tapp Robyn , Atan Denize , Doney Alexander , allen Naomi , Littlejohns Thomas , Sergouniotis Panagiotis , Black Graeme ,   GIGA study group, Kanyaro Neema , Ntomoka Cyprian , Massaga Julius J. , Ikungura Joyce K. ,   23 and Me Research Team, Agee Michelle , Aslibekyan Stella , Bell Robert K. , Bryc Katarzyna , Clark Sarah K. , Elson Sarah L. , Fletez-Brant Kipper , Fontanillas Pierre , Furlotte Nicholas A. , Gandhi Pooja M. , Heilbron Karl , Hicks Barry , Hinds David A. , Huber Karen E. , Jewett Ethan M. , Jiang Yunxuan , Kleinman Aaron , Lin Keng-Han , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , McManus Kimberly F. , Mountain Joanna L. , Mozaffari Sahar V. , Nandakumar Priyanka , Noblin Elizabeth S. , Northover Carrie A. M. , O’Connell Jared , Pitts Steven J. , Poznik G. David , Sathirapongsasuti J. Fah , Shastri Anjali J. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Tunney Robert J. , Vacic Vladimir , Zare Amir S. , Tamiya Gen , Shiga Yukihiro , Yamamoto Masayuki , Nakazawa Toru , Currant Hannah , Birney Ewan , Wang Xin , Auton Adam , Lupton Michelle K. , Martin Nicholas G. , Ashaye Adeyinka , Olawoye Olusola , Williams Susan E. , Akafo Stephen , Ramsay Michele , Hashimoto Kazuki , Kamatani Yoichiro , Akiyama Masato , Momozawa Yukihide , Foster Paul J. , Khaw Peng T. , Morgan James E. , Strouthidis Nicholas G. , Kraft Peter , Kang Jae H. , Pang Chi Pui , Pasutto Francesca , Mitchell Paul , Lotery Andrew J. , Palotie Aarno , van Duijn Cornelia , Haines Jonathan L. , Hammond Chris , Pasquale Louis R. , Klaver Caroline C. W. , Hauser Michael , Khor Chiea Chuen , Mackey David A. , Kubo Michiaki , Cheng Ching-Yu , Craig Jamie E. , MacGregor Stuart , Wiggs Janey L. 
Published: February 2021

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.