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Nat Genet. 2016 May;48(5):556-62. doi: 10.1038/ng.3540. Epub 2016 Apr 4.

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

Khor CC1,2,3, Do T4, Jia H5, Nakano M6, George R7, Abu-Amero K8,9, Duvesh R10, Chen LJ11, Li Z1, Nongpiur ME2, Perera SA2, Qiao C5, Wong HT12, Sakai H13, Barbosa de Melo M14, Lee MC2, Chan AS2, Azhany Y15, Dao TL4, Ikeda Y16, Perez-Grossmann RA17, Zarnowski T18, Day AC19,20,21, Jonas JB22, Tam PO11, Tran TA23, Ayub H24, Akhtar F25, Micheal S26, Chew PT27, Aljasim LA28, Dada T29, Luu TT30, Awadalla MS31, Kitnarong N32, Wanichwecharungruang B33,34, Aung YY35, Mohamed-Noor J36, Vijayan S10, Sarangapani S37, Husain R2,38, Jap A2,38, Baskaran M2, Goh D2, Su DH2, Wang H5, Yong VK12, Yip LW12, Trinh TB23, Makornwattana M39, Nguyen TT40, Leuenberger EU41,42, Park KH43, Wiyogo WA44,45, Kumar RS46, Tello C47, Kurimoto Y48, Thapa SS49, Pathanapitoon K50, Salmon JF51, Sohn YH52, Fea A53, Ozaki M54,55, Lai JS56, Tantisevi V57, Khaing CC58, Mizoguchi T59, Nakano S60, Kim CY61, Tang G62, Fan S63, Wu R64, Meng H65, Nguyen TT4, Tran TD4, Ueno M16, Martinez JM66, Ramli N67,68, Aung YM69,70, Reyes RD71,72, Vernon SA73,74, Fang SK75, Xie Z1, Chen XY1, Foo JN1, Sim KS1, Wong TT2, Quek DT2, Venkatesh R76, Kavitha S76, Krishnadas SR77, Soumittra N37, Shantha B7, Lim BA12, Ogle J12, de Vasconcellos JP78, Costa VP77, Abe RY77, de Souza BB14, Sng CC27, Aquino MC27, Kosior-Jarecka E18, Fong GB79, Tamanaja VC80, Fujita R81, Jiang Y19,20,21, Waseem N19,21, Low S19,20,21, Pham HN23, Al-Shahwan S28, Craven ER28,82, Khan MI83, Dada R29, Mohanty K29, Faiq MA29, Hewitt AW84,85, Burdon KP31,84, Gan EH36, Prutthipongsit A39, Patthanathamrongkasem T39, Catacutan MA41, Felarca IR41, Liao CS41, Rusmayani E44, Istiantoro VW44, Consolandi G53, Pignata G53, Lavia C53, Rojanapongpun P57, Mangkornkanokpong L86, Chansangpetch S86, Chan JC87, Choy BN56, Shum JW56, Than HM88, Oo KT69,70, Han AT69,70, Yong VH2, Ng XY2, Goh SR2, Chong YF2, Hibberd ML1, Seielstad M89, Png E1, Dunstan SJ90,91, Chau NV92, Bei J93,94, Zeng YX93,94,95, Karkey A96, Basnyat B96, Pasutto F97, Paoli D98, Frezzotti P99, Wang JJ100, Mitchell P100, Fingert JH101,102, Allingham RR2,103, Hauser MA2,103,104, Lim ST105, Chew SH106, Ebstein RP107, Sakuntabhai A108,109, Park KH110, Ahn J111, Boland G112, Snippe H112, Stead R73, Quino R71, Zaw SN69,70, Lukasik U18, Shetty R46, Zahari M67,68, Bae HW61, Oo NL58, Kubota T60, Manassakorn A57, Ho WL86, Dallorto L53, Hwang YH52, Kiire CA51, Kuroda M48, Djamal ZE44, Peregrino JI41, Ghosh A46,113, Jeoung JW43, Hoan TS40, Srisamran N39, Sandragasu T36, Set SH35, Doan VH30, Bhattacharya SS21, Ho CL2, Tan DT2, Sihota R29, Loon SC27, Mori K16, Kinoshita S16, Hollander AI26,83, Qamar R24,114, Wang YX115, Teo YY1,116,115,116,117,118,119, Tai ES116,120, Hartleben-Matkin C121, Lozano-Giral D122, Saw SM2,116, Cheng CY2,27, Zenteno JC122,123, Pang CP11, Bui HT23, Hee O12, Craig JE31, Edward DP28,82, Yonahara M13, Neto JM78, Guevara-Fujita ML81, Xu L115, Ritch R47, Liza-Sharmini AT15, Wong TY2, Al-Obeidan S8, Do NH4, Sundaresan P10, Tham CC11, Foster PJ19,20,21, Vijaya L2,7, Tashiro K6, Vithana EN2, Wang N5,115, Aung T2,27.

Author information

1
Genome Institute of Singapore, A-STAR, Singapore.
2
Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke-National University of Singapore, Singapore.
3
Department of Biochemistry, National University of Singapore, Singapore.
4
Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
5
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.
6
Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
7
Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Sankara Nethralaya, Chennai, India.
8
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
9
Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA.
10
Department of Genetics, Aravind Medical Research Foundation, Madurai, India.
11
Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
12
Department of Ophthalmology, Tan Tock Seng Hospital, NHG Eye Institute, Singapore.
13
Department of Ophthalmology, University of the Ryukyus, Okinawa, Nishihara, Japan.
14
Center of Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil.
15
Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia and Hospital Universiti Sains Malaysia, Kelantan, Malaysia.
16
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
17
Instituto de Glaucoma y Catarata, Lima, Peru.
18
Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
19
NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK.
20
Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK.
21
Division of Genetics, UCL Institute of Ophthalmology, London, UK.
22
Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University Heidelberg, Heidelberg, Germany.
23
Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam.
24
Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
25
Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan.
26
Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.
27
Department of Ophthalmology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
28
King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
29
All India Institute of Medical Sciences, New Delhi, India.
30
Department of Glaucoma, Da Nang Eye Hospital, Da Nang City, Vietnam.
31
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
32
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
33
Glaucoma Services, Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand.
34
College of Medicine, Rangsit University, Bangkok, Thailand.
35
Mandalay Eye Department, Mandalay Eye ENT Hospital, University of Medicine Mandalay, Mandalay, Myanmar.
36
Department of Ophthalmology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
37
Vision Research Foundation, Sankara Nethralaya, Chennai, India.
38
Division of Ophthalmology, Changi General Hospital, Singapore.
39
Department of Ophthalmology, Thammasat University Faculty of Medicine, Rangsit, Thailand.
40
Eye Department, Viet Tiep General Hospital, Hai Phong, Vietnam.
41
Asian Eye Institute, Manila, Philippines.
42
Division of Ophthalmology, University of the East, Manila, Philippines.
43
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.
44
Glaucoma Service Jakarta Eye Center, Jakarta, Indonesia.
45
Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
46
Narayana Nethralaya Eye Hospital, Bangalore, India.
47
Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.
48
Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan.
49
Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology, Kathmandu, Nepal.
50
Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
51
Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
52
Department of Ophthalmology, Konyang University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, Republic of Korea.
53
Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy.
54
Ozaki Eye Hospital, Hyuga, Japan.
55
Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
56
Department of Ophthalmology, University of Hong Kong, Hong Kong, China.
57
Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
58
Department of Ophthalmology, No. 1 Defence Services General Hospital, Yangon, Myanmar.
59
Mizoguchi Eye Hospital, Sasebo, Japan.
60
Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan.
61
Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
62
Shijiazhuang First Eye Hospital, Shijiazhuang, China.
63
Handan Eye Hospital, Handan, China.
64
Eye Institute and Affiliated Xiamen Eye Center, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
65
Anyang Eye Hospital, Anyang, China.
66
Department of Ophthalmology, Pasig City General Hospital, Pasig City, Philippines.
67
University of Malaya, Eye Research Centre, Kuala Lumpur, Malaysia.
68
Department of Ophthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
69
Myanmar Eye Centre, Pun Hlaing Silom Hospital, Yangon, Myanmar.
70
Myanmar Eye Centre, Shwe La Min Hospital, Yangon, Myanmar.
71
Department of Ophthalmology/Glaucoma Section, Asian Hospital and Medical Center, Muntinlupa City, Philippines.
72
Binan Doctors Eye Center, Binan Doctors Hospital, Laguna, Philippines.
73
Department of Ophthalmology, University Hospital Nottingham, University of Nottingham, Nottingham, UK.
74
BMI Park Hospital Nottingham, Nottingham, UK.
75
International Specialist Eye Centre, Kuala Lumpur, Malaysia.
76
Glaucoma Clinic, Aravind Eye Hospital, Pondicherry, India.
77
Glaucoma Clinic, Aravind Eye Hospital, Madurai, India.
78
Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
79
Instituto de Ciencias Médicas, Lima, Peru.
80
Hospital Nacional Arzobispo Loayza, Lima, Peru.
81
Centro de Genética y Biología Molecular, Universidad de San Martín de Porres, Lima, Peru.
82
Wilmer Eye Institute, Johns Hopkins Hospital School of Medicine, Baltimore, Maryland, USA.
83
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
84
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
85
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
86
Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
87
Department of Ophthalmology, Queen Mary Hospital, Hong Kong, China.
88
Department of Ophthalmology, North Okkalarpa General Hospital, Yangon, Myanmar.
89
Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
90
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
91
Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
92
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
93
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
94
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
95
Peking Union Medical College, Beijing, China.
96
Oxford University Clinical Research Unit-Nepal, Patan Academy of Health Sciences, Patan Hospital, Patan, Nepal.
97
Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
98
Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy.
99
Department of Surgery, Section of Ophthalmology, University of Siena, Siena, Italy.
100
Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
101
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
102
Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA.
103
Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA.
104
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
105
Division of Medical Oncology, National Cancer Centre, Singapore.
106
Department of Economics, National University of Singapore, Singapore.
107
Department of Psychology, National University of Singapore, Singapore.
108
Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France.
109
Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France.
110
Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea.
111
Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
112
Department of Medical Microbiology and Virology, University Medical Center Utrecht, Utrecht, the Netherlands.
113
GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India.
114
Department of Biochemistry, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan.
115
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
116
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
117
Life Sciences Institute, National University of Singapore, Singapore.
118
National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.
119
Department of Statistics and Applied Probability, National University of Singapore, Singapore.
120
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
121
Department of Glaucoma, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico.
122
Department of Genetics, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico.
123
Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.

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.

PMID:
27064256
DOI:
10.1038/ng.3540
[Indexed for MEDLINE]

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