PMID- 27089177
OWN - NLM
STAT- MEDLINE
DCOM- 20170628
LR  - 20220330
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
VI  - 48
IP  - 6
DP  - 2016 Jun
TI  - A missense variant in FGD6 confers increased risk of polypoidal choroidal 
      vasculopathy.
PG  - 640-7
LID - 10.1038/ng.3546 [doi]
AB  - Polypoidal choroidal vasculopathy (PCV), a subtype of 'wet' age-related macular 
      degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. 
      In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk 
      factors for PCV are relatively unknown. Exome sequencing analysis of a Han 
      Chinese cohort followed by replication in four independent cohorts identified a 
      rare c.986A>G (p.Lys329Arg) variant in the FGD6 gene as significantly associated 
      with PCV (P = 2.19 x 10(-16), odds ratio (OR) = 2.12) but not with CNV (P = 0.26, 
      OR = 1.13). The intracellular localization of FGD6-Arg329 is distinct from that 
      of FGD6-Lys329. In vitro, FGD6 could regulate proangiogenic activity, and 
      oxidized phospholipids increased expression of FGD6. FGD6-Arg329 promoted more 
      abnormal vessel development in the mouse retina than FGD6-Lys329. Collectively, 
      our data suggest that oxidized phospholipids and FGD6-Arg329 might act 
      synergistically to increase susceptibility to PCV.
FAU - Huang, Lulin
AU  - Huang L
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China.
AD  - Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, 
      China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Zhang, Houbin
AU  - Zhang H
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Cheng, Ching-Yu
AU  - Cheng CY
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
AD  - Duke-National University of Singapore Graduate Medical School, Singapore.
FAU - Wen, Feng
AU  - Wen F
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Tam, Pancy O S
AU  - Tam PO
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhao, Peiquan
AU  - Zhao P
AD  - Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, 
      Shanghai, China.
FAU - Chen, Haoyu
AU  - Chen H
AUID- ORCID: 0000-0003-0676-4610
AD  - Joint Shantou International Eye Center, Shantou University and Chinese University 
      of Hong Kong, Shantou, China.
FAU - Li, Zheng
AU  - Li Z
AUID- ORCID: 0000-0002-7060-2213
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
AD  - Department of Human Genetics, Genome Institute of Singapore, Singapore.
FAU - Chen, Lijia
AU  - Chen L
AD  - Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Tai, Zhengfu
AU  - Tai Z
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China.
AD  - Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, 
      China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Yamashiro, Kenji
AU  - Yamashiro K
AUID- ORCID: 0000-0001-9354-8558
AD  - Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
FAU - Deng, Shaoping
AU  - Deng S
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Zhu, Xianjun
AU  - Zhu X
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Chen, Weiqi
AU  - Chen W
AD  - Joint Shantou International Eye Center, Shantou University and Chinese University 
      of Hong Kong, Shantou, China.
FAU - Cai, Li
AU  - Cai L
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Lu, Fang
AU  - Lu F
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Li, Yuanfeng
AU  - Li Y
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Cheung, Chui-Ming G
AU  - Cheung CM
AUID- ORCID: 0000-0003-3358-3516
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
FAU - Shi, Yi
AU  - Shi Y
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Miyake, Masahiro
AU  - Miyake M
AD  - Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
FAU - Lin, Yin
AU  - Lin Y
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Gong, Bo
AU  - Gong B
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Liu, Xiaoqi
AU  - Liu X
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Sim, Kar-Seng
AU  - Sim KS
AUID- ORCID: 0000-0002-3822-7759
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
AD  - Department of Human Genetics, Genome Institute of Singapore, Singapore.
FAU - Yang, Jiyun
AU  - Yang J
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Mori, Keisuke
AU  - Mori K
AD  - Department of Ophthalmology, Saitama Medical University, Iruma, Japan.
FAU - Zhang, Xiongzhe
AU  - Zhang X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Cackett, Peter D
AU  - Cackett PD
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Princess Alexandra Eye Pavilion, Edinburgh, UK.
FAU - Tsujikawa, Motokazu
AU  - Tsujikawa M
AD  - Department of Ophthalmology, Osaka University Medical School, Osaka, Japan.
FAU - Nishida, Kohji
AU  - Nishida K
AD  - Department of Ophthalmology, Osaka University Medical School, Osaka, Japan.
FAU - Hao, Fang
AU  - Hao F
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Ma, Shi
AU  - Ma S
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Lin, He
AU  - Lin H
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Cheng, Jing
AU  - Cheng J
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Fei, Ping
AU  - Fei P
AD  - Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, 
      Shanghai, China.
FAU - Lai, Timothy Y Y
AU  - Lai TY
AD  - Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Tang, Sibo
AU  - Tang S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Laude, Augustinus
AU  - Laude A
AD  - National Health care Group Eye Institute, Tan Tock Seng Hospital, Singapore.
FAU - Inoue, Satoshi
AU  - Inoue S
AD  - Division of Gene Regulation and Signal Transduction, Research Center for Genomic 
      Medicine, Saitama Medical University, Saitama, Japan.
FAU - Yeo, Ian Y
AU  - Yeo IY
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Duke-National University of Singapore Graduate Medical School, Singapore.
FAU - Sakurada, Yoichi
AU  - Sakurada Y
AD  - Department of Surgery, Division of Ophthalmology, Kobe University Graduate School 
      of Medicine, Kobe, Japan.
FAU - Zhou, Yu
AU  - Zhou Y
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Iijima, Hiroyuki
AU  - Iijima H
AD  - Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
FAU - Honda, Shigeru
AU  - Honda S
AD  - Department of Surgery, Division of Ophthalmology, Kobe University Graduate School 
      of Medicine, Kobe, Japan.
FAU - Lei, Chuntao
AU  - Lei C
AD  - Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan 
      Provincial People's Hospital, Chengdu, China.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
FAU - Zheng, Hong
AU  - Zheng H
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Jiang, Dan
AU  - Jiang D
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Zhu, Xiong
AU  - Zhu X
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
FAU - Wong, Tien-Ying
AU  - Wong TY
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
AD  - Duke-National University of Singapore Graduate Medical School, Singapore.
FAU - Khor, Chiea-Chuen
AU  - Khor CC
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
AD  - Department of Human Genetics, Genome Institute of Singapore, Singapore.
FAU - Pang, Chi-Pui
AU  - Pang CP
AD  - Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Yoshimura, Nagahisa
AU  - Yoshimura N
AD  - Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
FAU - Yang, Zhenglin
AU  - Yang Z
AD  - Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences 
      and Sichuan Provincial People's Hospital, School of Medicine, University of 
      Electronic Science and Technology of China, Chengdu, China.
AD  - Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China.
AD  - Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, 
      China.
AD  - Center of Information in Biomedicine, University of Electronic Science and 
      Technology of China, Chengdu, China.
LA  - eng
PT  - Journal Article
DEP - 20160418
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (FGD6 protein, human)
RN  - 0 (Guanine Nucleotide Exchange Factors)
SB  - IM
MH  - Cells, Cultured
MH  - China
MH  - Cohort Studies
MH  - Endothelium, Vascular/cytology/metabolism
MH  - Ethnicity
MH  - Gene Expression Profiling
MH  - Guanine Nucleotide Exchange Factors/*genetics/metabolism
MH  - Humans
MH  - *Mutation, Missense
MH  - Polymorphism, Single Nucleotide
MH  - Subcellular Fractions/metabolism
MH  - Wet Macular Degeneration/*genetics
EDAT- 2016/04/19 06:00
MHDA- 2017/06/29 06:00
CRDT- 2016/04/19 06:00
PHST- 2015/12/30 00:00 [received]
PHST- 2016/03/16 00:00 [accepted]
PHST- 2016/04/19 06:00 [entrez]
PHST- 2016/04/19 06:00 [pubmed]
PHST- 2017/06/29 06:00 [medline]
AID - ng.3546 [pii]
AID - 10.1038/ng.3546 [doi]
PST - ppublish
SO  - Nat Genet. 2016 Jun;48(6):640-7. doi: 10.1038/ng.3546. Epub 2016 Apr 18.