title: A common variant near TGFBR3 is associated with primary open angle glaucoma.
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.
authors: Singapore Eye Research Institute, Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Zheng
authors: Z
authors: Li
authors: Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA.
authors: R Rand
authors: RR
authors: Allingham
authors: Department of Genomic Medical Sciences.
authors: Masakazu
authors: M
authors: Nakano
authors: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors: Liyun
authors: L
authors: Jia
authors: Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical School.
authors: Yuhong
authors: Y
authors: Chen
authors: Department of Ophthalmology.
authors: Yoko
authors: Y
authors: Ikeda
authors: Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors: Baskaran
authors: B
authors: Mani
authors: Department of Ophthalmology and Visual Sciences, The Chinese Uuniversity of Hong Kong Eye Hospital, Hong Kong, China.
authors: Li-Jia
authors: LJ
authors: Chen
authors: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Seoul Korea.
authors: Changwon
authors: C
authors: Kee
authors: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, London, UK.
authors: David F
authors: DF
authors: Garway-Heath
authors: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Sarangapani
authors: S
authors: Sripriya
authors: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Sendai, Japan.
authors: Nobuo
authors: N
authors: Fuse
authors: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, USA.
authors: Khaled K
authors: KK
authors: Abu-Amero
authors: Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou University, Shantou, China.
authors: Chukai
authors: C
authors: Huang
authors: Department of Genetics, Aravind Medical Research Foundation, Madurai, Tamilnadu, India.
authors: Prasanthi
authors: P
authors: Namburi
authors: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia, Department of Ophthalmology, Flinders University, Adelaide, Australia.
authors: Kathryn
authors: K
authors: Burdon
authors: Singapore Eye Research Institute, Duke-NUS Graduate Medical School, Singapore, Singapore, Singapore National Eye Center, Singapore, Singapore.
authors: Shamira A
authors: SA
authors: Perera
authors: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors: Puya
authors: P
authors: Gharahkhani
authors: 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.
authors: Ying
authors: Y
authors: Lin
authors: Department of Ophthalmology.
authors: Morio
authors: M
authors: Ueno
authors: Ozaki Eye Hospital, 1-15, Kamezaki, Hyuga, Miyazaki 883-0066, Japan.
authors: Mineo
authors: M
authors: Ozaki
authors: Mizoguchi Eye Hospital, 6-13 Tawara-machi, Sasebo, Nagasaki 857-0016, Japan.
authors: Takanori
authors: T
authors: Mizoguchi
authors: Glaucoma Services, Aravind Eye Hospital, Madurai, Tamilnadu, India.
authors: Subbiah Ramasamy
authors: SR
authors: Krishnadas
authors: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors: Essam A
authors: EA
authors: Osman
authors: Singapore Eye Research Institute.
authors: Mei Chin
authors: MC
authors: Lee
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
authors: Anita S Y
authors: AS
authors: Chan
authors: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors: Liza-Sharmini A
authors: LS
authors: Tajudin
authors: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors: Tan
authors: T
authors: Do
authors: Ophthalmology Department.
authors: Aurelien
authors: A
authors: Goncalves
authors: Biochemistry Department, Angers University Hospital, Angers, France.
authors: Pascal
authors: P
authors: Reynier
authors: Department of Ophthalmology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Hong
authors: H
authors: Zhang
authors: Huntingdon Glaucoma Diagnostic & Research Centre, Hinchingbrooke Hospital, Huntingdon, UK.
authors: Rupert
authors: R
authors: Bourne
authors: Singapore National Eye Center, Singapore, Singapore.
authors: David
authors: D
authors: Goh
authors: Norfolk & Norwich University Hospital NHS Trust, Norwich, UK.
authors: David
authors: D
authors: Broadway
authors: Singapore National Eye Center, Singapore, Singapore.
authors: Rahat
authors: R
authors: Husain
authors: Heart of UK NHS Foundation Trust, Birmingham, UK.
authors: Anil K
authors: AK
authors: Negi
authors: Singapore National Eye Center, Singapore, Singapore.
authors: Daniel H
authors: DH
authors: Su
authors: Singapore National Eye Center, Singapore, Singapore.
authors: Ching-Lin
authors: CL
authors: Ho
authors: School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, Queen's University Belfast, Northern Ireland, UK.
authors: Augusto Azuara
authors: AA
authors: Blanco
authors: Department of Ophthalmology and Visual Sciences, The Chinese Uuniversity of Hong Kong Eye Hospital, Hong Kong, China.
authors: Christopher K S
authors: CK
authors: Leung
authors: Singapore Eye Research Institute, Duke-NUS Graduate Medical School, Singapore, Singapore, Singapore National Eye Center, Singapore, Singapore.
authors: Tina T
authors: TT
authors: Wong
authors: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors: Azhany
authors: A
authors: Yakub
authors: Department of Medicine, Duke University Medical Center, Durham, NC, USA, Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia.
authors: Yutao
authors: Y
authors: Liu
authors: Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors: Monisha E
authors: ME
authors: Nongpiur
authors: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Seoul Korea.
authors: Jong Chul
authors: JC
authors: Han
authors: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors: Do Nhu
authors: DN
authors: Hon
authors: Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Balekudaru
authors: B
authors: Shantha
authors: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors: Bowen
authors: B
authors: Zhao
authors: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors: Jinghong
authors: J
authors: Sang
authors: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors: NiHong
authors: N
authors: Zhang
authors: Department of Genomic Medical Sciences.
authors: Ryuichi
authors: R
authors: Sato
authors: Department of Medical Statistics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Kengo
authors: K
authors: Yoshii
authors: Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
authors: Songhomita
authors: S
authors: Panda-Jonas
authors: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors: Allison E
authors: AE
authors: Ashley Koch
authors: Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA.
authors: Leon W
authors: LW
authors: Herndon
authors: Department of Ophthalmology and Visual Sciences.
authors: Sayoko E
authors: SE
authors: Moroi
authors: Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA.
authors: Pratap
authors: P
authors: Challa
authors: Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Jia Nee
authors: JN
authors: Foo
authors: State Key Laboratory of Oncology in Southern China, Guangzhou, China, Department of Experimental Research, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
authors: Jin-Xin
authors: JX
authors: Bei
authors: State Key Laboratory of Oncology in Southern China, Guangzhou, China, Department of Experimental Research, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
authors: Yi-Xin
authors: YX
authors: Zeng
authors: 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.
authors: Cameron P
authors: CP
authors: Simmons
authors: Clinical Research Unit, Oxford University, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam.
authors: Tran Nguyen
authors: TN
authors: Bich Chau
authors: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Philomenadin Ferdinamarie
authors: PF
authors: Sharmila
authors: Singapore Eye Research Institute.
authors: Merwyn
authors: M
authors: Chew
authors: Singapore Eye Research Institute.
authors: Blanche
authors: B
authors: Lim
authors: Department of Ophthalmology and Visual Sciences, The Chinese Uuniversity of Hong Kong Eye Hospital, Hong Kong, China.
authors: Pansy O S
authors: PO
authors: Tam
authors: Singapore Eye Research Institute.
authors: Elaine
authors: E
authors: Chua
authors: Singapore Eye Research Institute.
authors: Xiao Yu
authors: XY
authors: Ng
authors: Singapore Eye Research Institute.
authors: Victor H K
authors: VH
authors: Yong
authors: Singapore Eye Research Institute.
authors: Yaan Fun
authors: YF
authors: Chong
authors: Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Wee Yang
authors: WY
authors: Meah
authors: Department of Genetics, Aravind Medical Research Foundation, Madurai, Tamilnadu, India.
authors: Saravanan
authors: S
authors: Vijayan
authors: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Seoul Korea.
authors: Sohn
authors: S
authors: Seongsoo
authors: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors: Wang
authors: W
authors: Xu
authors: Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors: Yik Ying
authors: YY
authors: Teo
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors: Jessica N
authors: JN
authors: Cooke Bailey
authors: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors: Jae H
authors: JH
authors: Kang
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors: Jonathan L
authors: JL
authors: Haines
authors: 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.
authors: Ching Yu
authors: CY
authors: Cheng
authors: Singapore Eye Research Institute, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors: Seang-Mei
authors: SM
authors: Saw
authors: Department of Medicine, National University Health System & National University of Singapore, Singapore.
authors: E-Shyong
authors: ES
authors: Tai
authors: Department of Ophthalmology and Visual Sciences, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
authors: Julia E
authors: JE
authors: Richards
authors: Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary, New York, NY, USA.
authors: Robert
authors: R
authors: Ritch
authors: Eye Doctors of Washington DC, Washington, DC, USA.
authors: Douglas E
authors: DE
authors: Gaasterland
authors: 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.
authors: Louis R
authors: LR
authors: Pasquale
authors: Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Jianjun
authors: J
authors: Liu
authors: Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
authors: Jost B
authors: JB
authors: Jonas
authors: Singapore Eye Research Institute, Duke-NUS Graduate Medical School, Singapore, Singapore, Singapore National Eye Center, Singapore, Singapore.
authors: Dan
authors: D
authors: Milea
authors: Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Ronnie
authors: R
authors: George
authors: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors: Saleh A
authors: SA
authors: Al-Obeidan
authors: Department of Ophthalmology.
authors: Kazuhiko
authors: K
authors: Mori
authors: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors: Stuart
authors: S
authors: Macgregor
authors: 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.
authors: Alex W
authors: AW
authors: Hewitt
authors: Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Christopher A
authors: CA
authors: Girkin
authors: Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou University, Shantou, China.
authors: Mingzhi
authors: M
authors: Zhang
authors: Department of Genetics, Aravind Medical Research Foundation, Madurai, Tamilnadu, India.
authors: Periasamy
authors: P
authors: Sundaresan
authors: Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Lingam
authors: L
authors: Vijaya
authors: 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.
authors: David A
authors: DA
authors: Mackey
authors: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine.
authors: Tien Yin
authors: TY
authors: Wong
authors: Department of Ophthalmology, Flinders University, Adelaide, Australia.
authors: Jamie E
authors: JE
authors: Craig
authors: 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.
authors: Xinghuai
authors: X
authors: Sun
authors: Department of Ophthalmology.
authors: Shigeru
authors: S
authors: Kinoshita
authors: Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Janey L
authors: JL
authors: Wiggs
authors: 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.
authors: Chiea-Chuen
authors: CC
authors: Khor
authors: 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.
authors: Zhenglin
authors: Z
authors: Yang
authors: Department of Ophthalmology and Visual Sciences, The Chinese Uuniversity of Hong Kong Eye Hospital, Hong Kong, China.
authors: Chi Pui
authors: CP
authors: Pang
authors: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors: Ningli
authors: N
authors: Wang
authors: Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors: Michael A
authors: MA
authors: Hauser
authors: Department of Genomic Medical Sciences.
authors: Kei
authors: K
authors: Tashiro
authors: 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.
authors: Tin
authors: T
authors: Aung
authors: 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.
authors: Eranga N
authors: EN
authors: Vithana
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan