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

Author

Listed:
  • Lv-Zhen Huang

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • 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
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Ching-Yu Cheng

    (Singapore Eye Research Institute
    Duke-National University of Singapore Graduate School of Medicine
    National University of Singapore and National University Health System
    Singapore National Eye Center)

  • 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
    Singapore National Eye Center)

  • Yu-Sheng Wang

    (Singapore National Eye Center
    Xijing Hospital, Fourth Military Medical University)

  • Chun-Fang Zhang

    (Peking University People’s Hospital)

  • Yu-Jing Bai

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Jing Hou

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Xiao-Li Chen

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Yun Qi

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Shan-Shan Li

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Yao-Yao Sun

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Jun-Pu Mei

    (BGI-Shenzhen)

  • Yong Cheng

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Wen-Zhen Yu

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • 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
    Eye and ENT hospital of Fudan University)

  • Xing-Huai Sun

    (Shanghai Medical College Fudan University
    Eye and ENT hospital of Fudan University)

  • Xiang-Jia Zhu

    (Shanghai Medical College Fudan University
    Eye and ENT hospital of Fudan University)

  • De-Fen Shen

    (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
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

  • Nagahisa Yoshimura

    (Kyoto University Graduate School of Medicine)

  • Chi Pui Pang

    (the Chinese University of Hong Kong)

  • Tien Yin Wong

    (Singapore Eye Research Institute
    Duke-National University of Singapore Graduate School of Medicine
    National University of Singapore and National University Health System
    Singapore National Eye Center)

  • Chiea Chuen Khor

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Genome Institute of Singapore
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System)

  • Kang Zhang

    (Institute for Genomic Medicine and Shiley Eye Center
    University of California at San Diego, La Jolla)

  • Peng Zhou

    (Shanghai Medical College Fudan University
    Eye and ENT hospital of Fudan University
    Parkway Health Hongqiao Medical Center)

  • Xiao-Xin Li

    (Key Laboratory of Vision Loss and Restoration, Ministry of Education of China
    Peking University People’s Hospital
    Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases)

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.

Suggested Citation

  • 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, 2015. "Whole-exome sequencing implicates UBE3D in age-related macular degeneration in East Asian populations," Nature Communications, Nature, vol. 6(1), pages 1-6, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7687
    DOI: 10.1038/ncomms7687
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    Cited by:

    1. Qiao Fan & Hengtong Li & Xiaomeng Wang & Yih-Chung Tham & Kelvin Yi Chong Teo & Masayuki Yasuda & Weng Khong Lim & Yuet Ping Kwan & Jing Xian Teo & Ching-Jou Chen & Li Jia Chen & Jeeyun Ahn & Sonia Da, 2023. "Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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