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Seven new loci associated with age-related macular degeneration

2013; Nature Portfolio; Volume: 45; Issue: 4 Linguagem: Inglês

10.1038/ng.2578

1546-1718

Lars G. Fritsche, Wei Chen, Matthew Schu, Brian L. Yaspan, Yi Yu, Guðmar Þorleifsson, Donald J. Zack, Satoshi Arakawa, Valentina Cipriani, Stephan Ripke, Robert P. Igo, Gabriëlle H.S. Buitendijk, Xueling Sim, Daniel E. Weeks, Robyn H. Guymer, Joanna E. Merriam, Peter J. Francis, Gregory Hannum, Anita Agarwal, Ana Maria Armbrecht, Isabelle Audo, Tin Aung, Gaetano R. Barile, Mustapha Benchaboune, Alan C. Bird, Paul N. Bishop, Kari Branham, Matthew Brooks, Alexander J. Brucker, William H. Cade, Melinda Cain, Peter A. Campochiaro, Chi Chao Chan, Ching‐Yu Cheng, Emily Y. Chew, Kimberly Chin, Itay Chowers, David Clayton, Radu Cojocaru, Yvette P. Conley, Belinda K. Cornes, Mark J. Daly, Baljean Dhillon, Albert O. Edwards, Εvangelos Εvangelou, Jesen Fagerness, Henry Ferreyra, James S. Friedman, Ásbjörg Geirsdóttir, Ronnie George, Christian Gieger, Neel Gupta, Stephanie A. Hagstrom, Simon Harding, Christos Haritoglou, John R. Heckenlively, Frank G. Holz, Guy Hughes, John P. A. Ioannidis, Tatsuro Ishibashi, Peronne Joseph, Gyungah Jun, Yoichiro Kamatani, Nicholas Katsanis, Claudia N. Keilhauer, Jane C. Khan, Ivana K. Kim, Yutaka Kiyohara, Barbara E.K. Klein, Ronald Klein, Jaclyn L. Kovach, Igor Kozak, Clara J. Lee, Kristine E. Lee, Peter Lichtner, Andrew Lotery, Thomas Meitinger, Paul Mitchell, Saddek Mohand‐Saïd, Anthony T. Moore, Denise J. Morgan, Margaux A. Morrison, Chelsea E. Myers, Adam C. Naj, Yusuke Nakamura, Yukinori Okada, Anton Orlin, Maria Carolina Ortube, Mohammad Othman, Chris Pappas, Kyu Hyung Park, Gayle J. Pauer, Neal S. Peachey, Olivier Poch, Rinki Ratna Priya, Robyn Reynolds, Andrea J. Richardson, Raymond Ripp, Guenther Rudolph, Euijung Ryu, José‐Alain Sahel, Debra A. Schaumberg, Hendrik P. N. Scholl, Stephen G. Schwartz, William K. Scott, Humma Shahid, Haraldur Sigurðsson, Giuliana Silvestri, Theru A. Sivakumaran, R. Theodore Smith, Lucia Sobrin, Eric H. Souied, Dwight Stambolian, Hreinn Stefánsson, Gwen M. Sturgill-Short, Atsushi Takahashi, Nirubol Tosakulwong, Barbara Truitt, Evangelia E. Tsironi, André G. Uitterlinden, Cornelia M. van Duijn, Lingam Vijaya, Johannes R. Vingerling, Eranga N. Vithana, Andrew R. Webster, H.-Erich Wichmann, Thomas W. Winkler, Tien Yin Wong, Alan F. Wright, Diana Zélénika, Ming Zhang, Ling Zhao, Kang Zhang, Michael L. Klein, Gregory S. Hageman, Mark G. Lathrop, Hreinn Stefánsson, Rando Allikmets, Paul N. Baird, Michael B. Gorin, Jie Jin Wang, Caroline C. W. Klaver, Johanna M. Seddon, Margaret A. Pericak‐Vance, Sudha K. Iyengar, John R.W. Yates, Anand Swaroop, Bernhard H. F. Weber, Michiaki Kubo, Margaret M. DeAngelis, Thierry Léveillard, Unnur Þorsteinsdóttir, Jonathan L. Haines, Lindsay A. Farrer, Iris M. Heid, Gonçalo R. Abecasis,

Retinal Development and Disorders

Gonçalo Abecasis and colleagues report a large-scale meta-analysis of genome-wide association studies for age-related macular degeneration (AMD), including over 17,100 advanced cases and 60,000 controls. They identify seven loci newly associated with AMD and report pathway analysis that shows enrichment in the complement system and atherosclerosis signaling. Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10−8. These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10−8 for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.