Seven new loci associated with age-related macular degeneration.
Seven new loci associated with age-related macular degeneration.
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DOI：
10.1038/ng.2578
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发表时间：
2013-04
期刊：
影响因子：
30.8
通讯作者：
Abecasis, Goncalo R.
中科院分区：
文献类型：
--
作者：
Fritsche, Lars G.;Chen, Wei;Schu, Matthew;Yaspan, Brian L.;Yu, Yi;Thorleifsson, Gudmar;Zack, Donald J.;Arakawa, Satoshi;Cipriani, Valentina;Ripke, Stephan;Igo, Robert P., Jr.;Buitendijk, Gabrielle H. S.;Sim, Xueling;Weeks, Daniel E.;Guymer, Robyn H.;Merriam, Joanna E.;Francis, Peter J.;Hannum, Gregory;Agarwal, Anita;Armbrecht, Ana Maria;Audo, Isabelle;Aung, Tin;Barile, Gaetano R.;Benchaboune, Mustapha;Bird, Alan C.;Bishop, Paul N.;Branham, Kari E.;Brooks, Matthew;Brucker, Alexander J.;Cade, William H.;Cain, Melinda S.;Campochiaroll, Peter A.;Chan, Chi-Chao;Cheng, Ching-Yu;Chew, Emily Y.;Chin, Kimberly A.;Chowers, Itay;Clayton, David G.;Cojocaru, Radu;Conley, Yvette P.;Cornes, Belinda K.;Daly, Mark J.;Dhillon, Baljean;Edwards, Albert;Evangelou, Evangelos;Fagemess, Jesen;Ferreyra, Henry A.;Friedman, James S.;Geirsdottir, Asbjorg;George, Ronnie J.;Gieger, Christian;Gupta, Neel;Hagstrom, Stephanie A.;Harding, Simon P.;Haritoglou, Christos;Heckenlively, John R.;Hoz, Frank G.;Hughes, Guy;Ioannidis, John P. A.;Ishibashi, Tatsuro;Joseph, Peronne;Jun, Gyungah;Kamatani, Yoichiro;Katsanis, Nicholas;Keilhauer, Claudia N.;Khan, Jane C.;Kim, Ivana K.;Kiyohara, Yutaka;Klein, Barbara E. K.;Klein, Ronald;Kovach, Jaclyn L.;Kozak, Igor;Lee, Clara J.;Lee, Kristine E.;Lichtner, Peter;Lotery, Andrew J.;Meitinger, Thomas;Mitchell, Paul;Mohand-Saied, Saddek;Moore, Anthony T.;Morgan, Denise J.;Morrison, Margaux A.;Myers, Chelsea E.;Naj, Adam C.;Nakamura, Yusuke;Okada, Yukinori;Orlin, Anton;Ortube, M. Carolina;Othman, Mohammad I.;Pappas, Chris;Park, Kyu Hyung;Pauer, Gayle J. T.;Peachey, Neal S.;Poch, Olivier;Priya, Rinki Ratna;Reynolds, Robyn;Richardson, Andrea J.;Ripp, Raymond;Rudolph, Guenther;Ryu, Euijung;Sahel, Jose-Alain;Schaumberg, Debra A.;Scholl, Hendrik P. N.;Schwartz, Stephen G.;Scott, William K.;Shahid, Humma;Sigurdsson, Haraldur;Silvestri, Giuliana;Sivakumaran, Theru A.;Smith, R. Theodore;Sobrin, Lucia;Souied, Eric H.;Stambolian, Dwight E.;Stefansson, Hreinn;Sturgill-Short, Gwen M.;Takahashi, Atsushi;Tosakulwong, Nirubol;Truitt, Barbara J.;Tsironi, Evangelia E.;Uitterlinden, Andre G.;van Duijn, Cornelia M.;Vijaya, Lingam;Vingerling, Johannes R.;Vithana, Eranga N.;Webster, Andrew R.;Wichmann, H-Erich;Winkler, Thomas W.;Wong, Tien Y.;Wright, Alan F.;Zelenika, Diana;Zhang, Ming;Zhao, Ling;Zhang, Kang;Klein, Michael L.;Hageman, Gregory S.;Lathrop, G. Mark;Stefansson, Kari;Allikmets, Rando;Baird, Paul N.;Gorin, Michael B.;Wang, Jie Jin;Klaver, Caroline C. W.;Seddon, Johanna M.;Pericak-Vance, Margaret A.;Iyengar, Sudha K.;Yates, John R. W.;Swaroop, Anand;Weber, Bernhard H. F.;Kubo, Michiaki;DeAngelis, Margaret M.;Leveillard, Thierry;Thorsteinsdottir, Unnur;Haines, Jonathan L.;Farrer, Lindsay A.;Heid, Iris M.;Abecasis, Goncalo R.
视网膜相关性黄斑变性（AMD）是老年人失明的常见原因。为了加速对AMD生物学的理解并帮助设计新的治疗方法，我们进行了一项全基因组协作关联研究，检查了超过17，100例晚期AMD病例和超过60，000例欧洲和亚洲血统的对照。我们确定了19个与AMD相关的基因组位点，p<5×10−8，并富集了参与补体活性调节、脂质代谢、细胞外基质重塑和血管生成的基因。我们的研究结果包括7个位点首次达到p<5×10−8，靠近基因COL 8A 1/FILIP 1 L，IER 3/DDR 1，SLC 16 A8，TGFBR 1，RAD 51 B，ADAMTS 9/MIR 548 A2和B3 GALTL。结合所有位点的SNP的遗传风险评分显示出相似的良好能力，以区分所有样本中的病例和对照。我们的发现为AMD的生物学、遗传学和治疗研究提供了新的方向。
Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
5.2
作者：
Fagerness, Jesen A.;Maller, Julian B.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
30.8
作者：
Hughes, Anne E.;Orr, Nick;Chakravarthy, Usha
通讯作者：
Chakravarthy, Usha
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA