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Nat Commun. 2015 Mar 31;6:6689. doi: 10.1038/ncomms7689.

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.

Author information

1
1] Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan [2] Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
2
Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
3
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
4
1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Department of Pediatrics, National University of Singapore, Singapore 119077, Singapore [4] Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
5
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.
6
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama 2360027, Japan.
7
Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 6570013, Japan.
8
Faculty of Medicine, University of Split, Split 21000, Croatia.
9
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK.
10
Centre for Population Health Sciences, Medical School, Teviot, Edinburgh EH8 9AG, UK.
11
Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
12
1] Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama 2360027, Japan [2] Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
13
1] Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia [2] Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia 6009, Australia.
14
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
15
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, Sichuan 610072, China.
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, Sichuan 610072, China [2] School of Medicine, University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China [3] Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan 610072, China.
17
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
18
Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
19
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 1130034, Japan.
20
1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
21
1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
22
1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore [2] Department of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
23
1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [2] Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 1130034, Japan [3] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
24
1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [3] Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
25
Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan.
26
Department of Genome Informatics, Kyoto University School of Public Health, Kyoto, Japan.
27
Department of Medical Ethics, Kyoto University School of Public Health, Kyoto, Japan.

Abstract

Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

PMID:
25823570
DOI:
10.1038/ncomms7689
[Indexed for MEDLINE]

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