Nat Commun. 2015 Apr 15;6:6687. doi: 10.1038/ncomms7687.

Author information

1
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.
2
Department of Abdominal Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
3
BGI-Shenzhen, Shenzhen 518083, China.
4
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.
5
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
6
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong 999077, China.
7
Department of Ophthalmology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China.
8
1] Singapore Eye Research Institute, Singapore 169856, Singapore [2] Singapore National Eye Center, Singapore 168751, Singapore.
9
1] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China [2] Singapore National Eye Center, Singapore 168751, Singapore.
10
Department of Clinical Epidemiology, Peking University People’s Hospital, Beijing 100044, China.
11
Beijing View Solid Biotechnology, Beijing 100034, China.
12
Shanghai Medical College Fudan University, Shanghai 200032, China.
13
1] Shanghai Medical College Fudan University, Shanghai 200032, China [2] Department of Ophthalmology, Eye and ENT hospital of Fudan University, Shanghai 200433, China.
14
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
15
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.
16
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.
17
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.

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.

PMID:
25872646
DOI:
10.1038/ncomms7687