title: Whole-exome sequencing implicates UBE3D in age-related macular degeneration in East Asian populations.
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.
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Lv-Zhen
authors: LZ
authors: Huang
authors: Department of Abdominal Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
authors: Ying-Jie
authors: YJ
authors: Li
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Xue-Feng
authors: XF
authors: Xie
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Jing-Jing
authors: JJ
authors: Zhang
authors: 1] Singapore Eye Research Institute, Singapore 169856, Singapore [2] Duke-National University of Singapore Graduate School of Medicine, Singapore 169857, Singapore [3] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [4] Singapore National Eye Center, Singapore 168751, Singapore.
authors: Ching-Yu
authors: CY
authors: Cheng
authors: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors: Kenji
authors: K
authors: Yamashiro
authors: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong 999077, China.
authors: Li-Jia
authors: LJ
authors: Chen
authors: Department of Ophthalmology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China.
authors: Xiao-Yun
authors: XY
authors: Ma
authors: 1] Singapore Eye Research Institute, Singapore 169856, Singapore [2] Singapore National Eye Center, Singapore 168751, Singapore.
authors: Chui Ming G
authors: CM
authors: Cheung
authors: 1] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China [2] Singapore National Eye Center, Singapore 168751, Singapore.
authors: Yu-Sheng
authors: YS
authors: Wang
authors: Department of Clinical Epidemiology, Peking University People's Hospital, Beijing 100044, China.
authors: Chun-Fang
authors: CF
authors: Zhang
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Yu-Jing
authors: YJ
authors: Bai
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Jing
authors: J
authors: Hou
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Xiao-Li
authors: XL
authors: Chen
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Yun
authors: Y
authors: Qi
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Shan-Shan
authors: SS
authors: Li
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Yao-Yao
authors: YY
authors: Sun
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Jun-Pu
authors: JP
authors: Mei
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Yong
authors: Y
authors: Cheng
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Wen-Zhen
authors: WZ
authors: Yu
authors: Beijing View Solid Biotechnology, Beijing 100034, China.
authors: Xiong-Bing
authors: XB
authors: Hu
authors: Beijing View Solid Biotechnology, Beijing 100034, China.
authors: Feng-Feng
authors: FF
authors: Zhuang
authors: Shanghai Medical College Fudan University, Shanghai 200032, China.
authors: Lei
authors: L
authors: Fan
authors: 1] Shanghai Medical College Fudan University, Shanghai 200032, China [2] Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai 200433, China.
authors: Yi
authors: Y
authors: Lu
authors: 1] Shanghai Medical College Fudan University, Shanghai 200032, China [2] Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai 200433, China.
authors: Xing-Huai
authors: XH
authors: Sun
authors: 1] Shanghai Medical College Fudan University, Shanghai 200032, China [2] Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai 200433, China.
authors: Xiang-Jia
authors: XJ
authors: Zhu
authors: National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: De-Fen
authors: DF
authors: Shen
authors: National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Chi-Chao
authors: CC
authors: Chan
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Ming-Wei
authors: MW
authors: Zhao
authors: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
authors: Nagahisa
authors: N
authors: Yoshimura
authors: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong 999077, China.
authors: Chi Pui
authors: CP
authors: Pang
authors: 1] Singapore Eye Research Institute, Singapore 169856, Singapore [2] Duke-National University of Singapore Graduate School of Medicine, Singapore 169857, Singapore [3] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [4] Singapore National Eye Center, Singapore 168751, Singapore.
authors: Tien Yin
authors: TY
authors: Wong
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore [3] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore.
authors: Chiea Chuen
authors: CC
authors: Khor
authors: 1] Institute for Genomic Medicine and Shiley Eye Center, La Jolla, California 92093, USA [2] University of California at San Diego, La Jolla, California 92093, USA.
authors: Kang
authors: K
authors: Zhang
authors: 1] Shanghai Medical College Fudan University, Shanghai 200032, China [2] Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai 200433, China [3] Parkway Health Hongqiao Medical Center, Shanghai 201101, China.
authors: Peng
authors: P
authors: Zhou
authors: 1] Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China [2] Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China [3] Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China.
authors: Xiao-Xin
authors: XX
authors: Li
mesh_terms: D000368:Aged; D000792:Angiography; D000818:Animals; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D004396:Coloring Agents; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006723:Hong Kong; D006801:Humans; D007208:Indocyanine Green; D007564:Japan; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055213:Retinal Pigment Epithelium / Q000473:pathology; D017422:Sequence Analysis, DNA; D012846:Singapore; D041623:Tomography, Optical Coherence; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004396:Coloring Agents; C502845:UBE3D protein, human; D044767:Ubiquitin-Protein Ligases; D007208:Indocyanine Green