New loci and coding variants confer risk for age-related macular degeneration in East Asians.
New loci and coding variants confer risk for age-related macular degeneration in East Asians.
复制标题
DOI：
10.1038/ncomms7063
复制
发表时间：
2015-01-28
影响因子：
16.6
通讯作者：
Khor, Chiea Chuen
中科院分区：
文献类型：
--
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
视网膜相关性黄斑变性（AMD）是失明的主要原因，但在欧洲人和亚洲人中表现不同。在这里，我们对2，119例渗出性AMD患者和5，691例对照进行了全基因组和外显子组关联研究，并在4，226例患者和10，289例对照中进行了独立复制，所有患者均为东亚血统，作为亚洲人AMD遗传学（GAMA）联盟的一部分。我们发现CETP Asp442Gly（rs2303790）（一种东亚特异性突变）与AMD风险增加之间存在强相关性（比值比（OR）=1.70，P=5.60 × 10−22）。AMD风险等位基因（442Gly），已知可预防冠心病，在东亚人（n= 7，102）中使HDL胆固醇水平增加0.17 mmol l−1（P=5.82 × 10−21）。我们还发现了三个新的AMD基因座：C6orf223 Ala231Ala（OR=0.78，P=6.19 × 10−18），SLC44A4 Asp47Val（OR=1.27，P=1.08 × 10−11）和FGD6 Gln257Arg（OR=0.87，P=2.85 × 10−8）。我们的研究结果表明，一些遗传位点赋予AMD的易感性在东亚人与欧洲人共享，但AMD在东亚人也可能有一个独特的基因签名。 视网膜相关性黄斑变性（AMD）是全球范围内致盲的主要原因。在这里，作者对AMD进行了两阶段的全基因组关联研究，并确定了三个新的AMD风险位点，突出了东亚人和欧洲人共同和不同的遗传基础。
Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10−22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l−1 (P=5.82 × 10−21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10−18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10−11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10−8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature. Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.
登录
查看更多内容
与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
--
作者：
Cheung, Chui Ming Gemmy;Tai, E. Shyong;Wong, Tien Y.
通讯作者：
Wong, Tien Y.
影响因子：
30.8
作者：
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
通讯作者：
Cupples LA