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A common variant near TGFBR3 is associated with primary open angle glaucoma

Li Z 1 , Allingham RR 2 , Nakano M 3 , Jia L 4 , Chen Y 5 , Ikeda Y 6 Show all authors , Mani B 7 , Chen LJ 8 , Kee C 9 , Garway-Heath DF 10 , Sripriya S 11 , Fuse N 12 , Abu-Amero KK 13 , Huang C 14 , Namburi P 15 , Burdon K 16 , Perera SA 17 , Gharahkhani P 18 , Lin Y 19 , Ueno M 6 , Ozaki M 20 , Mizoguchi T 21 , Krishnadas SR 22 , Osman EA 23 , Lee MC 24 , Chan AS 25 , Tajudin LS 26 , Do T 27 , Goncalves A 28 , Reynier P 29 , Zhang H 30 , Bourne R 31 , Goh D 32 , Broadway D 33 , Husain R 32 , Negi AK 34 , Su DH 32 , Ho CL 32 , Blanco AA 35 , Leung CK 8 , Wong TT 17 , Yakub A 26 , Liu Y 36 , Nongpiur ME 7 , Han JC 9 , Hon DN 27 , Shantha B 37 , Zhao B 4 , Sang J 4 , Zhang N 4 , Sato R 3 , Yoshii K 38 , Panda-Jonas S 39 , Ashley Koch AE 40 , Herndon LW 2 , Moroi SE 41 , Challa P 2 , Foo JN 42 , Bei JX 43 , Zeng YX 43 , Simmons CP 44 , Bich Chau TN 45 , Sharmila PF 11 , Chew M 24 , Lim B 24 , Tam PO 8 , Chua E 24 , Ng XY 24 , Yong VH 24 , Chong YF 24 , Meah WY 42 , Vijayan S 15 , Seongsoo S 9 , Xu W 46 , Teo YY 47 , Cooke Bailey JN 48 , Kang JH 49 , Haines JL 48 , Cheng CY 50 , Saw SM 51 , Tai ES 52 , ICAARE-Glaucoma Consortium , NEIGHBORHOOD Consortium , Richards JE 53 , Ritch R 54 , Gaasterland DE 55 , Pasquale LR 56 , Liu J 42 , Jonas JB 39 , Milea D 17 , George R 37 , Al-Obeidan SA 23 , Mori K 6 , Macgregor S 18 , Hewitt AW 57 , Girkin CA 58 , Zhang M 14 , Sundaresan P 15 , Vijaya L 37 , Mackey DA 59 , Wong TY 60 , Craig JE 61 , Sun X 62 , Kinoshita S 6 , Wiggs JL 58 , Khor CC 63 , Yang Z 64 , Pang CP 8 , Wang N 4 , Hauser MA 65 , Tashiro K 3 , Aung T 66 , Vithana EN 67

Affiliations 

  • 1 Singapore Eye Research Institute, Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore
  • 2 Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA
  • 3 Department of Genomic Medical Sciences
  • 4 Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China
  • 5 Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical School
  • 6 Department of Ophthalmology
  • 7 Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore
  • 8 Department of Ophthalmology and Visual Sciences, The Chinese Uuniversity of Hong Kong Eye Hospital, Hong Kong, China
  • 9 Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Seoul Korea
  • 10 National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, London, UK
  • 11 SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • 12 Department of Integrative Genomics, Tohoku Medical Megabank Organization, Sendai, Japan
  • 13 Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, USA
  • 14 Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou University, Shantou, China
  • 15 Department of Genetics, Aravind Medical Research Foundation, Madurai, Tamilnadu, India
  • 16 Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia, Department of Ophthalmology, Flinders University, Adelaide, Australia
  • 17 Singapore Eye Research Institute, Duke-NUS Graduate Medical School, Singapore, Singapore, Singapore National Eye Center, Singapore, Singapore
  • 18 Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  • 19 Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
  • 20 Ozaki Eye Hospital, 1-15, Kamezaki, Hyuga, Miyazaki 883-0066, Japan
  • 21 Mizoguchi Eye Hospital, 6-13 Tawara-machi, Sasebo, Nagasaki 857-0016, Japan
  • 22 Glaucoma Services, Aravind Eye Hospital, Madurai, Tamilnadu, India
  • 23 Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • 24 Singapore Eye Research Institute
  • 25 Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore
  • 26 Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia
  • 27 Vietnam National Institute of Ophthalmology, Hanoi, Vietnam
  • 28 Ophthalmology Department
  • 29 Biochemistry Department, Angers University Hospital, Angers, France
  • 30 Department of Ophthalmology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 31 Huntingdon Glaucoma Diagnostic & Research Centre, Hinchingbrooke Hospital, Huntingdon, UK
  • 32 Singapore National Eye Center, Singapore, Singapore
  • 33 Norfolk & Norwich University Hospital NHS Trust, Norwich, UK
  • 34 Heart of UK NHS Foundation Trust, Birmingham, UK
  • 35 School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, Queen's University Belfast, Northern Ireland, UK
  • 36 Department of Medicine, Duke University Medical Center, Durham, NC, USA, Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia
  • 37 Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • 38 Department of Medical Statistics, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 39 Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
  • 40 Department of Medicine, Duke University Medical Center, Durham, NC, USA
  • 41 Department of Ophthalmology and Visual Sciences
  • 42 Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore
  • 43 State Key Laboratory of Oncology in Southern China, Guangzhou, China, Department of Experimental Research, Sun Yat-Sen University Cancer Centre, Guangzhou, China
  • 44 Clinical Research Unit, Oxford University, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam, Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford OX3 7LJ, UK
  • 45 Clinical Research Unit, Oxford University, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam
  • 46 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 47 Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 48 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
  • 49 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
  • 50 Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore, Singapore National Eye Center, Singapore, Singapore
  • 51 Singapore Eye Research Institute, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 52 Department of Medicine, National University Health System & National University of Singapore, Singapore
  • 53 Department of Ophthalmology and Visual Sciences, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
  • 54 Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary, New York, NY, USA
  • 55 Eye Doctors of Washington DC, Washington, DC, USA
  • 56 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
  • 57 Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia, Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia
  • 58 Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, USA
  • 59 Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia, Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, WA, Australia
  • 60 Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine
  • 61 Department of Ophthalmology, Flinders University, Adelaide, Australia
  • 62 Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical School, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China, Myopia Key Laboratory of the Ministry of Health of China, Shanghai, China and
  • 63 Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine, eranga.n.v@sericom.sg khorcc@gis.a-star.edu.sg
  • 64 Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, Chinese Academy of Sciences, Sichuan Translational Medicine Hospital, Chengdu, China
  • 65 Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA, Department of Medicine, Duke University Medical Center, Durham, NC, USA
  • 66 Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore
  • 67 Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore, eranga.n.v@sericom.sg khorcc@gis.a-star.edu.sg
Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
PMID: 25861811 DOI: 10.1093/hmg/ddv128

Abstract

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

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

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