Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Chiea Chuen Khor (1, 2) , Tan Do (3) , Hongyan Jia (4) , Masakazu Nakano (5) , Ronnie George , Khaled Abu-Amero , Roopam Duvesh , Li Jia Chen , Zheng Li , Monisha E Nongpiur , Shamira A Perera , Chunyan Qiao , Hon-Tym Wong , Hiroshi Sakai , Mônica Barbosa De Melo , Mei-Chin Lee , Anita S Chan , Yaakub Azhany , Thi Lam Huong Dao , Yoko Ikeda , Rodolfo A Perez-Grossmann , Tomasz Zarnowski , Alexander C Day , Jost B Jonas , Pancy O S Tam , Tuan Anh Tran , Humaira Ayub , Farah Akhtar , Shazia Micheal , Paul T K Chew , Leyla A Aljasim , Tanuj Dada , Tam Thi Luu , Mona S Awadalla , Naris Kitnarong , Boonsong Wanichwecharungruang , Yee Yee Aung , Jelinar Mohamed-Noor , Saravanan Vijayan , Sripriya Sarangapani , Rahat Husain , Aliza Jap , Mani Baskaran , David Goh , Daniel H Su , Huaizhou Wang , Vernon K Yong , Leonard W Yip , Tuyet Bach Trinh , Manchima Makornwattana , Thanh Thu Nguyen , Edgar U Leuenberger , Ki-Ho Park , Widya Artini Wiyogo , Rajesh S Kumar , Celso Tello , Yasuo Kurimoto , Suman S Thapa , Kessara Pathanapitoon , John F Salmon , Yong Ho Sohn , Antonio Fea , Mineo Ozaki , Jimmy S M Lai , Visanee Tantisevi , Chaw Chaw Khaing , Takanori Mizoguchi , Satoko Nakano , Chan-Yun Kim , Guangxian Tang , Sujie Fan , Renyi Wu , Hailin Meng , Thi Thuy Giang Nguyen , Tien Dat Tran , Morio Ueno , Jose Maria Martinez , Norlina Ramli , Yin Mon Aung , Rigo Daniel Reyes , Stephen A Vernon , Seng Kheong Fang , Zhicheng Xie , Xiao Yin Chen , Jia Nee Foo , Kar Seng Sim , Tina T Wong , Desmond T Quek , Rengaraj Venkatesh , Srinivasan Kavitha , Subbiah R Krishnadas , Nagaswamy Soumittra , Balekudaru Shantha , Boon-Ang Lim , Jeanne Ogle , José P C De Vasconcellos , Vital P Costa , Ricardo y Abe , Bruno B De Souza , Chelvin C Sng , Maria C Aquino , Ewa Kosior-Jarecka , Guillermo Barreto Fong , Vania Castro Tamanaja , Ricardo Fujita , Yuzhen Jiang , Naushin Waseem , Sancy Low , Huan Nguyen Pham , Sami Al-Shahwan , E Randy Craven , Muhammad Imran Khan , Rrima Dada , Kuldeep Mohanty , Muneeb A Faiq , Alex W Hewitt , Kathryn P Burdon , Eng Hui Gan , Anuwat Prutthipongsit , Thipnapa Patthanathamrongkasem , Mary Ann T Catacutan , Irene R Felarca , Chona S Liao , Emma Rusmayani , Vira Wardhana Istiantoro , Giulia Consolandi , Giulia Pignata , Carlo Lavia , Prin Rojanapongpun , Lerprat Mangkornkanokpong , Sunee Chansangpetch , Jonathan C H Chan , Bonnie N K Choy , Jennifer W H Shum , Hlaing May Than , Khin Thida Oo , Aye Thi Han , Victor H Yong , Xiao-Yu Ng , Shuang Ru Goh , Yaan Fun Chong , Martin L Hibberd , Mark Seielstad , Eileen Png , Sarah J Dunstan , Nguyen van Vinh Chau , Jinxin Bei , Yi Xin Zeng , Abhilasha Karkey , Buddha Basnyat , Francesca Pasutto , Daniela Paoli , Paolo Frezzotti , Jie Jin Wang , Paul Mitchell , John H Fingert , R Rand Allingham , Michael A Hauser , Soon Thye Lim , Soo Hong Chew , Richard P Ebstein , Anavaj Sakuntabhai (6) , Kyu Hyung Park , Jeeyun Ahn , Greet Boland , Harm Snippe , Richard Stead , Raquel Quino , Su Nyunt Zaw , Urszula Lukasik , Rohit Shetty , Mimiwati Zahari , Hyoung Won Bae , Nay Lin Oo , Toshiaki Kubota , Anita Manassakorn , Wing Lau Ho , Laura Dallorto , Young Hoon Hwang , Christine A Kiire , Masako Kuroda , Zeiras Eka Djamal , Jovell Ian M Peregrino , Arkasubhra Ghosh , Jin Wook Jeoung , Tung S Hoan , Nuttamon Srisamran , Thayanithi Sandragasu , Saw Htoo Set , Vi Huyen Doan , Shomi S Bhattacharya , Ching-Lin Ho , Donald T Tan , Ramanjit Sihota , Seng-Chee Loon , Kazuhiko Mori , Shigeru Kinoshita , Anneke I Den Hollander , Raheel Qamar , Ya-Xing Wang , Yik y Teo , E-Shyong Tai , Curt Hartleben-Matkin , David Lozano-Giral , Seang Mei Saw , Ching-Yu Cheng , Juan C Zenteno , Chi Pui Pang , Huong T T Bui , Owen Hee , Jamie E Craig , Deepak P Edward , Michiko Yonahara , Jamil Miguel Neto , Maria L Guevara-Fujita , Liang Xu , Robert Ritch , Ahmad Tajudin Liza-Sharmini , Tien y Wong , Saleh Al-Obeidan , Nhu Hon Do , Periasamy Sundaresan , Clement C Tham , Paul J Foster , Lingam Vijaya , Kei Tashiro (5) , Eranga N Vithana (2) , Ningli Wang (4) , Tin Aung (2)

1 GIS - Genome Institute of Singapore
2 NUS - National University of Singapore
3 VNIO - Vietnam National Institute of Ophthalmology
4 Beijing Tongren Hospital
5 Kyoto University
6 Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Domains: Genetics

Chiea Chuen Khor, Tan Do, Hongyan Jia, Masakazu Nakano, Ronnie George, et al.. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nature Genetics, 2016, 48 (5), pp.556-562. ⟨10.1038/ng.3540⟩. ⟨pasteur-02083054⟩