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

Khor CC 1 , Do T 2 , Jia H 3 , Nakano M 4 , George R 5 , Abu-Amero K 6 Show all authors , Duvesh R 7 , Chen LJ 8 , Li Z 1 , Nongpiur ME 9 , Perera SA 9 , Qiao C 3 , Wong HT 10 , Sakai H 11 , Barbosa de Melo M 12 , Lee MC 9 , Chan AS 9 , Azhany Y 13 , Dao TL 2 , Ikeda Y 14 , Perez-Grossmann RA 15 , Zarnowski T 16 , Day AC 17 , Jonas JB 18 , Tam PO 8 , Tran TA 19 , Ayub H 20 , Akhtar F 21 , Micheal S 22 , Chew PT 23 , Aljasim LA 24 , Dada T 25 , Luu TT 26 , Awadalla MS 27 , Kitnarong N 28 , Wanichwecharungruang B 29 , Aung YY 30 , Mohamed-Noor J 31 , Vijayan S 7 , Sarangapani S 32 , Husain R 9 , Jap A 9 , Baskaran M 9 , Goh D 9 , Su DH 9 , Wang H 3 , Yong VK 10 , Yip LW 10 , Trinh TB 19 , Makornwattana M 33 , Nguyen TT 34 , Leuenberger EU 35 , Park KH 36 , Wiyogo WA 37 , Kumar RS 38 , Tello C 39 , Kurimoto Y 40 , Thapa SS 41 , Pathanapitoon K 42 , Salmon JF 43 , Sohn YH 44 , Fea A 45 , Ozaki M 46 , Lai JS 47 , Tantisevi V 48 , Khaing CC 49 , Mizoguchi T 50 , Nakano S 51 , Kim CY 52 , Tang G 53 , Fan S 54 , Wu R 55 , Meng H 56 , Nguyen TT 2 , Tran TD 2 , Ueno M 14 , Martinez JM 57 , Ramli N 58 , Aung YM 59 , Reyes RD 60 , Vernon SA 61 , Fang SK 62 , Xie Z 1 , Chen XY 1 , Foo JN 1 , Sim KS 1 , Wong TT 9 , Quek DT 9 , Venkatesh R 63 , Kavitha S 63 , Krishnadas SR 64 , Soumittra N 32 , Shantha B 5 , Lim BA 10 , Ogle J 10 , de Vasconcellos JP 65 , Costa VP 64 , Abe RY 64 , de Souza BB 12 , Sng CC 23 , Aquino MC 23 , Kosior-Jarecka E 16 , Fong GB 66 , Tamanaja VC 67 , Fujita R 68 , Jiang Y 17 , Waseem N 17 , Low S 17 , Pham HN 19 , Al-Shahwan S 24 , Craven ER 24 , Khan MI 69 , Dada R 25 , Mohanty K 25 , Faiq MA 25 , Hewitt AW 70 , Burdon KP 27 , Gan EH 31 , Prutthipongsit A 33 , Patthanathamrongkasem T 33 , Catacutan MA 35 , Felarca IR 35 , Liao CS 35 , Rusmayani E 37 , Istiantoro VW 37 , Consolandi G 45 , Pignata G 45 , Lavia C 45 , Rojanapongpun P 48 , Mangkornkanokpong L 71 , Chansangpetch S 71 , Chan JC 72 , Choy BN 47 , Shum JW 47 , Than HM 73 , Oo KT 59 , Han AT 59 , Yong VH 9 , Ng XY 9 , Goh SR 9 , Chong YF 9 , Hibberd ML 1 , Seielstad M 74 , Png E 1 , Dunstan SJ 75 , Chau NV 76 , Bei J 77 , Zeng YX 77 , Karkey A 78 , Basnyat B 78 , Pasutto F 79 , Paoli D 80 , Frezzotti P 81 , Wang JJ 82 , Mitchell P 82 , Fingert JH 83 , Allingham RR 9 , Hauser MA 9 , Lim ST 84 , Chew SH 85 , Ebstein RP 86 , Sakuntabhai A 87 , Park KH 88 , Ahn J 89 , Boland G 90 , Snippe H 90 , Stead R 61 , Quino R 60 , Zaw SN 59 , Lukasik U 16 , Shetty R 38 , Zahari M 58 , Bae HW 52 , Oo NL 49 , Kubota T 51 , Manassakorn A 48 , Ho WL 71 , Dallorto L 45 , Hwang YH 44 , Kiire CA 43 , Kuroda M 40 , Djamal ZE 37 , Peregrino JI 35 , Ghosh A 38 , Jeoung JW 36 , Hoan TS 34 , Srisamran N 33 , Sandragasu T 31 , Set SH 30 , Doan VH 26 , Bhattacharya SS 91 , Ho CL 9 , Tan DT 9 , Sihota R 25 , Loon SC 23 , Mori K 14 , Kinoshita S 14 , Hollander AI 22 , Qamar R 20 , Wang YX 92 , Teo YY 1 , Tai ES 93 , Hartleben-Matkin C 94 , Lozano-Giral D 95 , Saw SM 9 , Cheng CY 9 , Zenteno JC 95 , Pang CP 8 , Bui HT 19 , Hee O 10 , Craig JE 27 , Edward DP 24 , Yonahara M 11 , Neto JM 65 , Guevara-Fujita ML 68 , Xu L 92 , Ritch R 39 , Liza-Sharmini AT 13 , Wong TY 9 , Al-Obeidan S 6 , Do NH 2 , Sundaresan P 7 , Tham CC 8 , Foster PJ 17 , Vijaya L 9 , Tashiro K 4 , Vithana EN 9 , Wang N 3 , Aung T 9

Affiliations 

  • 1 Genome Institute of Singapore, A-STAR, Singapore
  • 2 Vietnam National Institute of Ophthalmology, Hanoi, Vietnam
  • 3 Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China
  • 4 Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 5 Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • 6 Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • 7 Department of Genetics, Aravind Medical Research Foundation, Madurai, India
  • 8 Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China
  • 9 Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke-National University of Singapore, Singapore
  • 10 Department of Ophthalmology, Tan Tock Seng Hospital, NHG Eye Institute, Singapore
  • 11 Department of Ophthalmology, University of the Ryukyus, Okinawa, Nishihara, Japan
  • 12 Center of Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil
  • 13 Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia and Hospital Universiti Sains Malaysia, Kelantan, Malaysia
  • 14 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 15 Instituto de Glaucoma y Catarata, Lima, Peru
  • 16 Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland
  • 17 NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK
  • 18 Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University Heidelberg, Heidelberg, Germany
  • 19 Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam
  • 20 Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
  • 21 Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan
  • 22 Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands
  • 23 Department of Ophthalmology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 24 King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  • 25 All India Institute of Medical Sciences, New Delhi, India
  • 26 Department of Glaucoma, Da Nang Eye Hospital, Da Nang City, Vietnam
  • 27 Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia
  • 28 Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 29 Glaucoma Services, Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand
  • 30 Mandalay Eye Department, Mandalay Eye ENT Hospital, University of Medicine Mandalay, Mandalay, Myanmar
  • 31 Department of Ophthalmology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 32 Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • 33 Department of Ophthalmology, Thammasat University Faculty of Medicine, Rangsit, Thailand
  • 34 Eye Department, Viet Tiep General Hospital, Hai Phong, Vietnam
  • 35 Asian Eye Institute, Manila, Philippines
  • 36 Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea
  • 37 Glaucoma Service Jakarta Eye Center, Jakarta, Indonesia
  • 38 Narayana Nethralaya Eye Hospital, Bangalore, India
  • 39 Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA
  • 40 Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan
  • 41 Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology, Kathmandu, Nepal
  • 42 Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  • 43 Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
  • 44 Department of Ophthalmology, Konyang University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, Republic of Korea
  • 45 Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy
  • 46 Ozaki Eye Hospital, Hyuga, Japan
  • 47 Department of Ophthalmology, University of Hong Kong, Hong Kong, China
  • 48 Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  • 49 Department of Ophthalmology, No. 1 Defence Services General Hospital, Yangon, Myanmar
  • 50 Mizoguchi Eye Hospital, Sasebo, Japan
  • 51 Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan
  • 52 Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea
  • 53 Shijiazhuang First Eye Hospital, Shijiazhuang, China
  • 54 Handan Eye Hospital, Handan, China
  • 55 Eye Institute and Affiliated Xiamen Eye Center, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China
  • 56 Anyang Eye Hospital, Anyang, China
  • 57 Department of Ophthalmology, Pasig City General Hospital, Pasig City, Philippines
  • 58 University of Malaya, Eye Research Centre, Kuala Lumpur, Malaysia
  • 59 Myanmar Eye Centre, Pun Hlaing Silom Hospital, Yangon, Myanmar
  • 60 Department of Ophthalmology/Glaucoma Section, Asian Hospital and Medical Center, Muntinlupa City, Philippines
  • 61 Department of Ophthalmology, University Hospital Nottingham, University of Nottingham, Nottingham, UK
  • 62 International Specialist Eye Centre, Kuala Lumpur, Malaysia
  • 63 Glaucoma Clinic, Aravind Eye Hospital, Pondicherry, India
  • 64 Glaucoma Clinic, Aravind Eye Hospital, Madurai, India
  • 65 Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
  • 66 Instituto de Ciencias Médicas, Lima, Peru
  • 67 Hospital Nacional Arzobispo Loayza, Lima, Peru
  • 68 Centro de Genética y Biología Molecular, Universidad de San Martín de Porres, Lima, Peru
  • 69 Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands
  • 70 Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  • 71 Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 72 Department of Ophthalmology, Queen Mary Hospital, Hong Kong, China
  • 73 Department of Ophthalmology, North Okkalarpa General Hospital, Yangon, Myanmar
  • 74 Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA
  • 75 Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
  • 76 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
  • 77 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
  • 78 Oxford University Clinical Research Unit-Nepal, Patan Academy of Health Sciences, Patan Hospital, Patan, Nepal
  • 79 Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
  • 80 Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy
  • 81 Department of Surgery, Section of Ophthalmology, University of Siena, Siena, Italy
  • 82 Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia
  • 83 Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
  • 84 Division of Medical Oncology, National Cancer Centre, Singapore
  • 85 Department of Economics, National University of Singapore, Singapore
  • 86 Department of Psychology, National University of Singapore, Singapore
  • 87 Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France
  • 88 Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea
  • 89 Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
  • 90 Department of Medical Microbiology and Virology, University Medical Center Utrecht, Utrecht, the Netherlands
  • 91 Division of Genetics, UCL Institute of Ophthalmology, London, UK
  • 92 Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
  • 93 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
  • 94 Department of Glaucoma, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico
  • 95 Department of Genetics, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico
Nat Genet, 2016 May;48(5):556-62.
PMID: 27064256 DOI: 10.1038/ng.3540

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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