A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.
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DOI：
10.1038/s41598-017-07526-9
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发表时间：
2017-08-03
影响因子：
4.6
通讯作者：
Yoshimura N
中科院分区：
文献类型：
--
作者：
Kawashima-Kumagai K;Yamashiro K;Yoshikawa M;Miyake M;Ming GCC;Fan Q;Koh JY;Saito M;Sugahara-Kuroda M;Oishi M;Akagi-Kurashige Y;Nakata I;Nakanishi H;Gotoh N;Oishi A;Tamura H;Ooto S;Tsujikawa A;Kurimoto Y;Sekiryu T;Matsuda F;Khor CC;Cheng CY;Wong TY;Yoshimura N
双侧新生血管性年龄相关性黄斑变性（AMD）比单侧新生血管性AMD给患者带来更多的障碍。虽然一些AMD易感基因已被评估其与双边性的关联，但关于双边性的全基因组关联研究（GWAS）很少报道。在本研究中，我们使用东亚新生血管性AMD病例进行GWAS。发现阶段比较了803例单侧和321例双侧日本病例之间的581，252个单核苷酸多态性（SNP），但没有SNP显示全基因组意义，而6个区域的SNP显示P值< 1.0 × 10−5，STON 1-GTF 2A 1 L/LHCGR/FSHR，PLXNA 1，CTNNA 3，ARMS 2/HTRA 1，LHFP和FLJ 38725。对这六个地区进行的第一项重复研究比较了36例双侧和132例单侧日本病例，证实了rs 4482537（STON 1-GTF 2A 1 L/LHCGR/FSHR）、rs 2284665（ARMS 2/HTRA 1）和rs 8002574（LHFP）与双侧性的显著相关性。在第二项重复研究中，比较了来自新加坡的24例双侧和78例单侧病例，rs 4482537（STON 1-GTF 2A 1 L/LHCGR/FSHR）仅显示出显著相关性。发现和复制研究的荟萃分析证实了rs 4482537（STON 1-GTF 2A 1 L/LHCGR/FSHR）的全基因组水平显著相关（P = 2.61 × 10−9），rs 2284665（ARMS 2/HTRA 1）和rs 8002574（LHFP）的强相关性（P = 5.76 × 10−7和9.73 × 10−7）。我们对新生血管性AMD双侧性的GWAS发现了新的遗传位点STON 1-GTF 2A 1 L/LHCGR/FSHR，并证实了先前报道的ARMS 2/HTRA 1的相关性。
Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10−5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10−9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10−7 and 9.73 × 10−7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.
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影响因子：
16.6
作者：
Cheng, Ching-Yu;Yamashiro, Kenji;Chen, Li Jia;Ahn, Jeeyun;Huang, Lulin;Huang, Lvzhen;Cheung, Chui Ming G.;Miyake, Masahiro;Cackett, Peter D.;Yeo, Ian Y.;Laude, Augustinus;Mathur, Ranjana;Pang, Junxiong;Sim, Kar Seng;Koh, Adrian H.;Chen, Peng;Lee, Shu Yen;Wong, Doric;Chan, Choi Mun;Loh, Boon Kwang;Sun, Yaoyao;Davila, Sonia;Nakata, Isao;Nakanishi, Hideo;Akagi-Kurashige, Yumiko;Gotoh, Norimoto;Tsujikawa, Akitaka;Matsuda, Fumihiko;Mori, Keisuke;Yoneya, Shin;Sakurada, Yoichi;Iijima, Hiroyuki;Iida, Tomohiro;Honda, Shigeru;Lai, Timothy Yuk Yau;Tam, Pancy Oi Sin;Chen, Haoyu;Tang, Shibo;Ding, Xiaoyan;Wen, Feng;Lu, Fang;Zhang, Xiongze;Shi, Yi;Zhao, Peiquan;Zhao, Bowen;Sang, Jinghong;Gong, Bo;Dorajoo, Rajkumar;Yuan, Jian-Min;Koh, Woon-Puay;van Dam, Rob M.;Friedlander, Yechiel;Lin, Ying;Hibberd, Martin L.;Foo, Jia Nee;Wang, Ningli;Wong, Chang Hua;Tan, Gavin S.;Park, Sang Jun;Bhargava, Mayuri;Gopal, Lingam;Naing, Thet;Liao, Jiemin;Ong, Peng Guan;Mitchell, Paul;Zhou, Peng;Xie, Xuefeng;Liang, Jinlong;Mei, Junpu;Jin, Xin;Saw, Seang-Mei;Ozaki, Mineo;Mizoguchi, Takanori;Kurimoto, Yasuo;Woo, Se Joon;Chung, Hum;Yu, Hyeong-Gon;Shin, Joo Young;Park, Dong Ho;Kim, In Taek;Chang, Woohyok;Sagong, Min;Lee, Sang-Joon;Kim, Hyun Woong;Lee, Ji Eun;Li, Yi;Liu, Jianjun;Teo, Yik Ying;Heng, Chew Kiat;Lim, Tock Han;Yang, Suk-Kyun;Song, Kyuyoung;Vithana, Eranga N.;Aung, Tin;Bei, Jin Xin;Zeng, Yi Xin;Tai, E. Shyong;Li, Xiao Xin;Yang, Zhenglin;Park, Kyu-Hyung;Pang, Chi Pui;Yoshimura, Nagahisa;Wong, Tien Yin;Khor, Chiea Chuen
通讯作者：
Khor, Chiea Chuen
影响因子：
4.6
作者：
Nakata I;Yamashiro K;Kawaguchi T;Nakanishi H;Akagi-Kurashige Y;Miyake M;Tsujikawa A;Yamada R;Matsuda F;Yoshimura N;Nagahama Study Group
通讯作者：
Nagahama Study Group
影响因子：
3.9
作者：
Ladas, ID;Rouvas, AA;Koutsandrea, CN
通讯作者：
Koutsandrea, CN
影响因子：
13.7
作者：
Maguire, Maureen G.;Daniel, Ebenezer;Martin, Daniel F.
通讯作者：
Martin, Daniel F.
影响因子：
1.8
作者：
Freeman, EE;Muñoz, B;West, SK
通讯作者：
West, SK