title: Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma.
abstract: We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.
authors.affiliation: 1] Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China. [2].
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [3].
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore. [3].
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: 1] Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [2].
authors.forename: Liyun
authors.initials: L
authors.lastname: Jia
authors.affiliation: China Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li Jia
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Shaohong
authors.initials: S
authors.lastname: Qian
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Mani
authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Luo
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
authors.forename: Celeste
authors.initials: C
authors.lastname: Guzman
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Christopher K S
authors.initials: CK
authors.lastname: Leung
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Cao
authors.affiliation: West High School, Salt Lake City, Utah, USA.
authors.forename: Quanyao
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Clement C Y
authors.initials: CC
authors.lastname: Tham
authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Yilian
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: China Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ningli
authors.initials: N
authors.lastname: Wang
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore. [3] Human Genetics, Genome Institute of Singapore, Singapore. [4].
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: 1] Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. [2].
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: 1] Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China. [2] State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China. [3] Myopia Key Laboratory of the Ministry of Health of China, Shanghai, China. [4].
authors.forename: Xinghuai
authors.initials: X
authors.lastname: Sun
authors.affiliation: 1] 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. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [3] Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China. [4].
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002681:China; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012846:Singapore; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human