title: Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.
abstract: Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
authors.affiliation: Singapore Eye Research Institute, 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: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, 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 Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Monisha E
authors.initials: ME
authors.lastname: Nongpiur
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Ronnie
authors.initials: R
authors.lastname: George
authors.affiliation: Department of Ophthalmology & Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors.forename: Tan
authors.initials: T
authors.lastname: Do
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Abu-Amero
authors.affiliation: Shantou University-Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Chor Kai
authors.initials: CK
authors.lastname: Huang
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, UK.
authors.forename: Sancy
authors.initials: S
authors.lastname: Low
authors.affiliation: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.
authors.forename: Liza-Sharmini A
authors.initials: LA
authors.lastname: Tajudin
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Shamira A
authors.initials: SA
authors.lastname: Perera
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.|Saw Swee Hock School of Public Health, 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 Medical University, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Ching-Lin
authors.initials: CL
authors.lastname: Ho
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore.
authors.forename: Kar Seng
authors.initials: KS
authors.lastname: Sim
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Xiamen Eye Centre, Xiamen University, Xiamen, China.
authors.forename: Ren-Yi
authors.initials: RY
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology & Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Clement C Y
authors.initials: CCY
authors.lastname: Tham
authors.affiliation: Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Paul T K
authors.initials: PTK
authors.lastname: Chew
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Su
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Francis T
authors.initials: FT
authors.lastname: Oen
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Sripriya
authors.initials: S
authors.lastname: Sarangapani
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Nagaswamy
authors.initials: N
authors.lastname: Soumittra
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Essam A
authors.initials: EA
authors.lastname: Osman
authors.affiliation: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore.
authors.forename: Hon-Tym
authors.initials: HT
authors.lastname: Wong
authors.affiliation: Xingtai Eye Hospital, Xingtai, China.
authors.forename: Guangxian
authors.initials: G
authors.lastname: Tang
authors.affiliation: Handan Eye Hospital, Handan, China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Fan
authors.affiliation: Anyang Eye Hospital, Anyang, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Meng
authors.affiliation: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors.forename: Dao T L
authors.initials: DTL
authors.lastname: Huong
authors.affiliation: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Mani
authors.initials: M
authors.lastname: Baskaran
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Balekudaru
authors.initials: B
authors.lastname: Shantha
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Vedam L
authors.initials: VL
authors.lastname: Ramprasad
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Govindasamy
authors.initials: G
authors.lastname: Kumaramanickavel
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Alicia C
authors.initials: AC
authors.lastname: How
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Kelvin Y
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Theru A
authors.initials: TA
authors.lastname: Sivakumaran
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Victor H K
authors.initials: VHK
authors.lastname: Yong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Serena M L
authors.initials: SML
authors.lastname: Ting
authors.affiliation: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tay
authors.affiliation: Centre for Molecular Epidemiology, National University of Singapore, Singapore.
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Raghavan
authors.initials: R
authors.lastname: Lavanya
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Zheng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Tina T
authors.initials: TT
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Seng-Chee
authors.initials: SC
authors.lastname: Loon
authors.affiliation: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore.
authors.forename: Vernon K Y
authors.initials: VKY
authors.lastname: Yong
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, UK.
authors.forename: Naushin
authors.initials: N
authors.lastname: Waseem
authors.affiliation: Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.
authors.forename: Azhany
authors.initials: A
authors.lastname: Yaakub
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.affiliation: Department of Opthamology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.affiliation: Department of Opthamology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.affiliation: Department of Ophthalmology & Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Dennis S C
authors.initials: DSC
authors.lastname: Lam
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, UK.
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.affiliation: Shantou University-Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Centre for Molecular Epidemiology, National University of Singapore, Singapore.
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
authors.forename: Jost B
authors.initials: JB
authors.lastname: Jonas
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Department of Medicine, National University Health System & National University of Singapore, Singapore.|Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.affiliation: Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
authors.forename: Do Nhu
authors.initials: DN
authors.lastname: Hon
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: Human Genetics, Genome Institute of Singapore, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tran Nguyen Bich
authors.initials: TNB
authors.lastname: Chau
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
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
authors.lastname: Zeng
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London (UCL) Institute of Ophthalmology, London, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Foster
authors.affiliation: Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Lingam
authors.initials: L
authors.lastname: Vijaya
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology & Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ningli
authors.initials: N
authors.lastname: Wang
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University Health System & National University of Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D024161:Collagen Type XI / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015812:Glaucoma, Angle-Closure / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C574182:COL11A1 protein, human; D002352:Carrier Proteins; D024161:Collagen Type XI; C533786:PLEKHA7 protein, human; D012097:Repressor Proteins; C497230:ST18 protein, human; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase