Seven new loci associated with age-related macular degeneration.

Seven new loci associated with age-related macular degeneration.

Nature genetics (2013-03-05)

Lars G Fritsche, Wei Chen, Matthew Schu, Brian L Yaspan, Yi Yu, Gudmar Thorleifsson, 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 E Branham, Matthew Brooks, Alexander J Brucker, William H Cade, Melinda S Cain, Peter A Campochiaro, Chi-Chao Chan, Ching-Yu Cheng, Emily Y Chew, Kimberly A Chin, Itay Chowers, David G Clayton, Radu Cojocaru, Yvette P Conley, Belinda K Cornes, Mark J Daly, Baljean Dhillon, Albert O Edwards, Evangelos Evangelou, Jesen Fagerness, Henry A Ferreyra, James S Friedman, Asbjorg Geirsdottir, Ronnie J George, Christian Gieger, Neel Gupta, Stephanie A Hagstrom, Simon P 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 J 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, M Carolina Ortube, Mohammad I Othman, Chris Pappas, Kyu Hyung Park, Gayle J T 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 Sigurdsson, Giuliana Silvestri, Theru A Sivakumaran, R Theodore Smith, Lucia Sobrin, Eric H Souied, Dwight E Stambolian, Hreinn Stefansson, Gwen M Sturgill-Short, Atsushi Takahashi, Nirubol Tosakulwong, Barbara J 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 Y Wong, Alan F Wright, Diana Zelenika, Ming Zhang, Ling Zhao, Kang Zhang, Michael L Klein, Gregory S Hageman, G Mark Lathrop, Kari Stefansson, 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 Thorsteinsdottir, Jonathan L Haines, Lindsay A Farrer, Iris M Heid, Gonçalo R Abecasis

PMID23455636

摘要

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.