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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

2013; Nature Portfolio; Volume: 45; Issue: 12 Linguagem: Inglês

10.1038/ng.2802

1546-1718

Jean‐Charles Lambert, Carla A. Ibrahim‐Verbaas, Denise Harold, Adam C. Naj, Rebecca Sims, Céline Bellenguez, Gyungah Jun, Anita L. DeStefano, Joshua C. Bis, Gary W. Beecham, Benjamin Grenier‐Boley, Giancarlo Russo, Tricia A. Thornton‐Wells, Nicola Jones, Albert V. Smith, Vincent Chouraki, Charlene Thomas, M. Arfan Ikram, Diana Zélénika, Badri N. Vardarajan, Yoichiro Kamatani, Chiao‐Feng Lin, Amy Gerrish, Helena Schmidt, Brian W. Kunkle, Melanie Dunstan, Agustı́n Ruiz, Marie‐Thérèse Bihoreau, Seung‐Hoan Choi, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Alfredo Ramı́rez, Olivier Hanon, Annette L. Fitzpatrick, Joseph D. Buxbaum, Dominique Campion, Paul K. Crane, Clinton T. Baldwin, Tim Becker, Vilmundur Guðnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Lorna M. Lopez, Philip L. De Jager, Vincent Deramecourt, Janet Johnston, Denis A. Evans, Simon Lovestone, Luc Letenneur, Francisco Jesús Morón, David C. Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison Goate, Nathalie Fiévet, Matthew J. Huentelman, Michael Gill, Kristelle Brown, M. Ilyas Kamboh, Lina Keller, Pascale Barberger‐Gateau, Bernadette McGuinness, Eric B. Larson, Robert C. Green, Amanda Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George‐Hyslop, Jordi Clarimón, Alberto Lleó, Antony Bayer, Debby W. Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petroula Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez‐García, Nick C. Fox, John Hardy, María Cándida Déniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Michelangelo Mancuso, Fiona E. Matthews, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, María J. Bullido, Francesco Panza, Paolo Caffarra, Benedetta Nacmias, John R. Gilbert, Manuel Mayhaus, Lars Lannfelt, Hákon Hákonarson, Sabrina Pichler, Minerva M. Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Álvarez, Fanggeng Zou, Otto Valladares, Steven G. Younkin, Eliécer Coto, Kara L. Hamilton‐Nelson, Wei Gu, Cristina Razquín, Pau Pástor, Ignacio Mateo, Michael J. Owen, Kelley M. Faber, Pálmi V. Jónsson, Onofre Combarros, Michael O’Donovan, Laura B. Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H. Mosley, David Bennett, Tamara B. Harris, Laura Fratiglioni, Clive Holmes, Renée F.A.G. de Bruijn, Peter Passmore, Thomas J. Montine, Karolien Bettens, Jerome I. Rotter, Alexis Brice, Kevin Morgan, Tatiana Foroud, Walter A. Kukull, Didier Hannequin, John Powell, Michael A. Nalls, Karen Ritchie, Kathryn L. Lunetta, John S.K. Kauwe, Eric Boerwinkle, Markus J. Riemenschneider, Merçé Boada, Mikko Hiltunen, Eden R. Martin, Reinhold Schmidt, Dan Rujescu, Li‐San Wang, Jean‐François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M. Nöthen, Caroline Graff, Bruce M. Psaty, Lesley Jones, Jonathan L. Haines, Peter Holmans, Mark Lathrop, Margaret A. Pericak‐Vance, Lenore J. Launer, Lindsay A. Farrer, Cornelia M. van Duijn, Christine Van Broeckhoven, Valentina Moskvina, Sudha Seshadri, Julie Williams, Gerard D. Schellenberg, Philippe Amouyel,

Bioinformatics and Genomic Networks

Philippe Amouyel, Julie Williams, Gerard Schellenberg, Sudha Seshadri and colleagues report a meta-analysis of genome-wide association studies for late-onset Alzheimer's disease in 17,008 cases and 37,154 controls with replication in an additional 8,572 cases and 11,312 controls. They identify 11 loci newly associated with Alzheimer's disease. Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.