Whole-exome sequencing implicates UBE3D in age-related macular degeneration in East Asian populations

Lv-Zhen Huang, Ying-Jie Li, Xue-Feng Xie, Jing-Jing Zhang, Ching-Yu Cheng, Kenji Yamashiro, Li-Jia Chen, Xiao-Yun Ma, Chui Ming G. Cheung, Yu-Sheng Wang, Chun-Fang Zhang, Yu-Jing Bai, Jing Hou, Xiao-Li Chen, Yun Qi, Shan-Shan Li, Yao-Yao Sun, Jun-Pu Mei, Yong Cheng, Wen-Zhen Yu, Xiong-Bing Hu, Feng-Feng Zhuang, Lei Fan, Yi Lu, Xing-Huai Sun, Xiang-Jia Zhu, Shen De-Fen, Chi-Chao Chan, Ming-Wei Zhao (), Nagahisa Yoshimura, Chi Pui Pang, Tien Yin Wong, Chiea Chuen Khor, Kang Zhang, Peng Zhou () and Xiao-Xin Li ()
Additional contact information
Lv-Zhen Huang: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Ying-Jie Li: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
Xue-Feng Xie: BGI-Shenzhen
Jing-Jing Zhang: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Ching-Yu Cheng: Singapore Eye Research Institute
Kenji Yamashiro: Kyoto University Graduate School of Medicine
Li-Jia Chen: the Chinese University of Hong Kong
Xiao-Yun Ma: Guanghua Integrative Medicine Hospital
Chui Ming G. Cheung: Singapore Eye Research Institute
Yu-Sheng Wang: Singapore National Eye Center
Chun-Fang Zhang: Peking University People’s Hospital
Yu-Jing Bai: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Jing Hou: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Xiao-Li Chen: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Yun Qi: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Shan-Shan Li: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Yao-Yao Sun: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Jun-Pu Mei: BGI-Shenzhen
Yong Cheng: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Wen-Zhen Yu: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Xiong-Bing Hu: Beijing View Solid Biotechnology
Feng-Feng Zhuang: Beijing View Solid Biotechnology
Lei Fan: Shanghai Medical College Fudan University
Yi Lu: Shanghai Medical College Fudan University
Xing-Huai Sun: Shanghai Medical College Fudan University
Xiang-Jia Zhu: Shanghai Medical College Fudan University
Shen De-Fen: National Eye Institute, National Institutes of Health
Chi-Chao Chan: National Eye Institute, National Institutes of Health
Ming-Wei Zhao: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Nagahisa Yoshimura: Kyoto University Graduate School of Medicine
Chi Pui Pang: the Chinese University of Hong Kong
Tien Yin Wong: Singapore Eye Research Institute
Chiea Chuen Khor: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
Kang Zhang: Institute for Genomic Medicine and Shiley Eye Center
Peng Zhou: Shanghai Medical College Fudan University
Xiao-Xin Li: Key Laboratory of Vision Loss and Restoration, Ministry of Education of China

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

Abstract: Abstract Age-related macular degeneration (AMD) is a leading cause of irreversible central blindness among the elderly worldwide. We use exome sequencing to analyse nonsynonymous single-nucleotide variants (SNVs) across the whole genome of 216 neovascular AMD cases and 1,553 controls. As a follow-up validation, we evaluate 3,772 neovascular AMD cases and 6,942 controls from five independent cohorts in the East Asian population. Here we show strong evidence of an association at a novel, missense SNV, rs7739323, which is located in the ubiquitin protein ligase E3D (UBE3D) gene (Pmeta=1.46 × 10−9, odds ratio (OR)=0.74, 95% confidence interval (CI): 0.63–0.88). Furthermore, ablation of the UBE3D protein lead to an abnormal amount of pigment granules deposited in retinal pigment epithelium microvilli area and an abnormal response on electroretinography (ERG) in UBE3D+/− heterozygous mice. Our findings indicate that the ubiquitin-proteasome system may play a role in the pathogenesis of neovascular AMD.

Date: 2015
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DOI: 10.1038/ncomms7687

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