title: Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.
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.
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.|Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Kenji
authors.identifier: http://orcid.org/0000-0001-9354-8558
authors.initials: K
authors.lastname: Yamashiro
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suda
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morooka
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Department of Pediatrics, National University of Singapore, Singapore 119077, Singapore.|Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.
authors.forename: Fan
authors.initials: F
authors.lastname: Qiao
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.|Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nakata
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.|Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Akagi-Kurashige
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Gotoh
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Akitaka
authors.initials: A
authors.lastname: Tsujikawa
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama 2360027, Japan.
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authors.affiliation: Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 6570013, Japan.
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authors.affiliation: Faculty of Medicine, University of Split, Split 21000, Croatia.
authors.forename: Ozen
authors.initials: O
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authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK.
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authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK.
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authors.initials: AF
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authors.affiliation: Centre for Population Health Sciences, Medical School, Teviot, Edinburgh EH8 9AG, UK.
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authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
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authors.initials: AJ
authors.lastname: Richardson
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
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authors.initials: M
authors.lastname: Schache
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama 2360027, Japan.|Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.|Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia 6009, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
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authors.initials: AW
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authors.initials: G
authors.lastname: Cuellar
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Luling
authors.initials: L
authors.lastname: Huang
authors.affiliation: 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.|School of Medicine, University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan 610072, China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
authors.forename: Kim Hung
authors.initials: KH
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authors.affiliation: Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
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authors.initials: PYP
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authors.affiliation: Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
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authors.initials: MKH
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authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR 99907, China.
authors.forename: Shea Ping
authors.identifier: http://orcid.org/0000-0002-2170-8185
authors.initials: SP
authors.lastname: Yip
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 1130034, Japan.
authors.forename: Muka
authors.initials: M
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authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 1130034, Japan.
authors.forename: Kyoko
authors.initials: K
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authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama 2360027, Japan.
authors.forename: Nobuhisa
authors.initials: N
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authors.affiliation: Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
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authors.initials: V
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authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.|Department of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 1130034, Japan.|Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.|Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 6068503, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D003315:Cornea / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C490675:WNT7B protein, human; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse
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