Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma

Yuhong Chen; Ying Lin; Eranga N Vithana; Liyun Jia; Xianbo Zuo; Tien Yin Wong; Li Jia Chen; Xianjun Zhu; Pancy O S Tam; Bo Gong; Shaohong Qian; Zheng Li; Xiaoqi Liu; Baskaran Mani; Qian Luo; Celeste Guzman; Christopher K S Leung; Xiaobo Li; Wenjun Cao; Quanyao Yang; Clement C Y Tham; Yilian Cheng; Xuejun Zhang; Ningli Wang; Tin Aung; Chiea Chuen Khor; Chi Pui Pang; Xinghuai Sun; Zhenglin Yang

doi:10.1038/ng.3078

Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma

Nat Genet. 2014 Oct;46(10):1115-9. doi: 10.1038/ng.3078. Epub 2014 Aug 31.

Authors

Yuhong Chen¹, Ying Lin², Eranga N Vithana³, Liyun Jia⁴, Xianbo Zuo⁵, Tien Yin Wong⁶, Li Jia Chen⁷, Xianjun Zhu⁸, Pancy O S Tam⁷, Bo Gong⁸, Shaohong Qian⁹, Zheng Li⁶, Xiaoqi Liu⁸, Baskaran Mani⁶, Qian Luo¹⁰, Celeste Guzman⁶, Christopher K S Leung⁷, Xiaobo Li⁸, Wenjun Cao⁹, Quanyao Yang¹¹, Clement C Y Tham⁷, Yilian Cheng¹⁰, Xuejun Zhang⁵, Ningli Wang¹², Tin Aung⁶, Chiea Chuen Khor¹³, Chi Pui Pang¹⁴, Xinghuai Sun¹⁵, Zhenglin Yang¹⁶

Affiliations

¹ 1] Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China. [2].
² 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].
³ 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].
⁴ 1] Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [2].
⁵ China Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China.
⁶ 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University Health System and National University of Singapore, Singapore.
⁷ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
⁸ 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.
⁹ Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
¹⁰ Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
¹¹ West High School, Salt Lake City, Utah, USA.
¹² Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
¹³ 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].
¹⁴ 1] Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. [2].
¹⁵ 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].
¹⁶ 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].

PMID: 25173107
DOI: 10.1038/ng.3078

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter 1 / genetics*
Adolescent
Adult
Aged
Aged, 80 and over
Asian People / genetics
China
Chromosomes, Human, Pair 16 / genetics
Chromosomes, Human, Pair 9 / genetics
Female
Gene Expression
Genetic Predisposition to Disease / ethnology
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study
Genotype
Glaucoma, Open-Angle / ethnology
Glaucoma, Open-Angle / genetics*
Humans
Linkage Disequilibrium
Male
Middle Aged
Phosphotransferases (Phosphomutases) / genetics*
Polymorphism, Single Nucleotide*
Principal Component Analysis
Reverse Transcriptase Polymerase Chain Reaction
Singapore
Young Adult

Substances

ABCA1 protein, human
ATP Binding Cassette Transporter 1
Phosphotransferases (Phosphomutases)
phosphomannomutase 2, human