title: ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
abstract: Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Monisha E
authors.initials: ME
authors.lastname: Nongpiur
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Infectious Diseases, Genome Institute of Singapore, Singapore; Human Genetics, Genome Institute of Singapore, Singapore; Department of Paediatrics, National University Health System & National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Hongyan
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authors.lastname: Jia
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.affiliation: Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Chunyan
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authors.lastname: Qiao
authors.affiliation: Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: K Saidas
authors.initials: KS
authors.lastname: Nair
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Ronnie
authors.initials: R
authors.lastname: George
authors.affiliation: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors.forename: Do
authors.initials: D
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authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Khaled
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authors.lastname: Abu-Amero
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Shamira A
authors.initials: SA
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authors.affiliation: Ozaki Eye Hospital, Hyuga, Japan.
authors.forename: Mineo
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authors.affiliation: Mizoguchi Eye Clinic, Sasebo, Japan.
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authors.affiliation: NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Sancy
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authors.affiliation: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Liza-Sharmini A
authors.initials: LS
authors.lastname: Tajudin
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
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authors.affiliation: Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
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authors.initials: CC
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authors.affiliation: Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Ileana
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authors.affiliation: Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Paul T K
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authors.affiliation: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore.
authors.forename: Hon-Tym
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authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
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authors.affiliation: Kobe Gen Hospital, Kobe, Japan.
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authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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authors.forename: Sujie
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authors.affiliation: Anyang Eye Hospital, Anyang, China.
authors.forename: Hailin
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authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Hua
authors.initials: H
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authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
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authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
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authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
authors.forename: Ya-Xing
authors.initials: YX
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Raghavan
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authors.lastname: Lavanya
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Ren-Yi
authors.initials: RY
authors.lastname: Wu
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Zheng
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Daniel H
authors.initials: DH
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authors.affiliation: Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Seng-Chee
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authors.affiliation: Duke University Medical Center, Durham, North Carolina, United States of America.
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authors.initials: RR
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authors.affiliation: Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Michael A
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authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
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authors.forename: Vedam L
authors.initials: VL
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authors.affiliation: NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.
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authors.lastname: Waseem
authors.affiliation: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Azhany
authors.initials: A
authors.lastname: Yaakub
authors.affiliation: Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Kee-Seng
authors.initials: KS
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authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
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authors.lastname: Kumaramanickavel
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
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authors.initials: TT
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.
authors.forename: Alicia C
authors.initials: AC
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authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tran Nguyen Bich
authors.initials: TN
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authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou, China; Department of Experimental Research, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou, China; Department of Experimental Research, Sun Yat-Sen University Cancer Centre, Guangzhou, China; Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Yi-Xin
authors.initials: YX
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authors.affiliation: NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Shomi S
authors.initials: SS
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authors.affiliation: Shantou University/Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Mingzhi
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authors.lastname: Zhang
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Donald T
authors.initials: DT
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authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
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authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Al-Obeidan
authors.affiliation: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors.forename: Do Nhu
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Department of Medicine, National University Health System & National University of Singapore, Singapore.
authors.forename: E-Shyong
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
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authors.forename: Jost B
authors.initials: JB
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
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authors.affiliation: Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Simon W M
authors.initials: SW
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authors.affiliation: Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China; Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ningli
authors.initials: N
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authors.affiliation: Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
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mesh_terms: D000867:Anterior Chamber / Q000378:metabolism / Q000473:pathology*; D044466:Asian People; D055106:Genome-Wide Association Study; D015812:Glaucoma, Angle-Closure / Q000235:genetics* / Q000473:pathology; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C120809:ABCC5 protein, human