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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
Abstract : 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.
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Submitted on : Thursday, March 28, 2019 - 4:36:36 PM
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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, Nature Publishing Group, 2016, 48 (5), pp.556-562. ⟨10.1038/ng.3540⟩. ⟨pasteur-02083054⟩

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