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

Masahiro Miyake, Kenji Yamashiro (), Yasuharu Tabara, Kenji Suda, Satoshi Morooka, Hideo Nakanishi, Chiea-Chuen Khor, Peng Chen, Fan Qiao, Isao Nakata, Yumiko Akagi-Kurashige, Norimoto Gotoh, Akitaka Tsujikawa, Akira Meguro, Sentaro Kusuhara, Ozen Polasek, Caroline Hayward, Alan F. Wright, Harry Campbell, Andrea J. Richardson, Maria Schache, Masaki Takeuchi, David A. Mackey, Alex W. Hewitt, Gabriel Cuellar, Yi Shi, Luling Huang, Zhenglin Yang, Kim Hung Leung, Patrick Y.P. Kao, Maurice K.H. Yap, Shea Ping Yip, Muka Moriyama, Kyoko Ohno-Matsui, Nobuhisa Mizuki, Stuart MacGregor, Veronique Vitart, Tin Aung, Seang-Mei Saw, E-Shyong Tai, Tien Yin Wong, Ching-Yu Cheng, Paul N. Baird, Ryo Yamada, Fumihiko Matsuda and Nagahisa Yoshimura
Additional contact information
Masahiro Miyake: Kyoto University Graduate School of Medicine
Kenji Yamashiro: Kyoto University Graduate School of Medicine
Yasuharu Tabara: Center for Genomic Medicine, Kyoto University Graduate School of Medicine
Kenji Suda: Kyoto University Graduate School of Medicine
Satoshi Morooka: Kyoto University Graduate School of Medicine
Hideo Nakanishi: Kyoto University Graduate School of Medicine
Chiea-Chuen Khor: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
Peng Chen: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
Fan Qiao: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
Isao Nakata: Kyoto University Graduate School of Medicine
Yumiko Akagi-Kurashige: Kyoto University Graduate School of Medicine
Norimoto Gotoh: Center for Genomic Medicine, Kyoto University Graduate School of Medicine
Akitaka Tsujikawa: Kyoto University Graduate School of Medicine
Akira Meguro: Yokohama City University Graduate School of Medicine
Sentaro Kusuhara: Kobe University Graduate School of Medicine
Ozen Polasek: Faculty of Medicine, University of Split
Caroline Hayward: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
Alan F. Wright: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
Harry Campbell: Centre for Population Health Sciences, Medical School, Teviot
Andrea J. Richardson: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital
Maria Schache: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital
Masaki Takeuchi: Yokohama City University Graduate School of Medicine
David A. Mackey: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital
Alex W. Hewitt: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital
Gabriel Cuellar: Statistical Genetics, QIMR Berghofer Medical Research Institute
Yi Shi: 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
Luling Huang: 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
Zhenglin Yang: 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
Kim Hung Leung: The Hong Kong Polytechnic University
Patrick Y.P. Kao: Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University
Maurice K.H. Yap: Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University
Shea Ping Yip: The Hong Kong Polytechnic University
Muka Moriyama: Tokyo Medical and Dental University
Kyoko Ohno-Matsui: Tokyo Medical and Dental University
Nobuhisa Mizuki: Yokohama City University Graduate School of Medicine
Stuart MacGregor: Statistical Genetics, QIMR Berghofer Medical Research Institute
Veronique Vitart: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
Tin Aung: National University of Singapore and National University Health System
Seang-Mei Saw: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
E-Shyong Tai: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
Tien Yin Wong: National University of Singapore and National University Health System
Ching-Yu Cheng: National University of Singapore and National University Health System
Paul N. Baird: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital
Ryo Yamada: Center for Genomic Medicine, Kyoto University Graduate School of Medicine
Fumihiko Matsuda: Center for Genomic Medicine, Kyoto University Graduate School of Medicine
Nagahisa Yoshimura: Kyoto University Graduate School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7689

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