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

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 Zelenika, Badri N. VardarajanYoichiro Kamatani, Chiao Feng Lin, Amy Gerrish, Helena Schmidt, Brian Kunkle, Nathalie Fiévet, Philippe Amouyel, Florence Pasquier, Vincent Deramecourt, Renee F.A.G. De Bruijn, Najaf Amin, Albert Hofman, Cornelia M. Van Duijn, Melanie L. Dunstan, Paul Hollingworth, Michael J. Owen, Michael C. O'Donovan, Lesley Jones, Peter A. Holmans, Valentina Moskvina, Julie Williams, Clinton Baldwin, Lindsay A. Farrer, Seung Hoan Choi, Kathryn L. Lunetta, Annette L. Fitzpatrick, Tamara B. Harris, Bruce M. Psaty, John R. Gilbert, Kara L. Hamilton-Nelson, Eden R. Martin, Margaret A. Pericak-Vance, Jonathan L. Haines, Vilmundur Gudnason, Palmi V. Jonsson, Gudny Eiriksdottir, Marie Thérèse Bihoreau, Mark Lathrop, Otto Valladares, Laura B. Cantwell, Li San Wang, Gerard D. Schellenberg, Agustin Ruiz, Mercè Boada, Christiane Reitz, Richard Mayeux, Alfredo Ramirez, Wolfgang Maier, Olivier Hanon, Walter A. Kukull, Joseph D. Buxbaum, Dominique Campion, David Wallon, Didier Hannequin, Paul K. Crane, Eric B. Larson, Tim Becker, Carlos Cruchaga, Alison M. Goate, David Craig, Janet A. Johnston, Bernadette Mc-Guinness, Stephen Todd, Peter Passmore, Claudine Berr, Karen Ritchie, Oscar L. Lopez, Philip L. De Jager, Denis Evans, Simon Lovestone, Petroula Proitsi, John F. Powell, Luc Letenneur, Pascale Barberger-Gateau, Carole Dufouil, Jean François Dartigues, Francisco J. Morón, David C. Rubinsztein, Peter St. George-Hyslop, Kristel Sleegers, Karolien Bettens, Christine Van Broeckhoven, Matthew J. Huentelman, Michael Gill, Kristelle Brown, Kevin Morgan, M. Ilyas Kamboh, Lina Keller, Laura Fratiglioni, Robert Green, Amanda J. Myers, Seth Love, Ekaterina Rogaeva, John Gallacher, Anthony Bayer, Jordi Clarimon, Alberto Lleo, Debby W. Tsuang, Lei Yu, David A. Bennett, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, John Collinge, Simon Mead, Sandro Sorbi, Benedetta Nacmias, Florentino Sanchez-Garcia, Maria Candida Deniz Naranjo, Nick C. Fox, John Hardy, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Michelangelo Mancuso, Fiona Matthews, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Harald Hampel, Alberto Pilotto, Maria Bullido, Francesco Panza, Paolo Caffarra, Manuel Mayhaus, Sabrina Pichler, Wei Gu, Matthias Riemenschneider, Lars Lannfelt, Martin Ingelsson, Hakon Hakonarson, Minerva M. Carrasquillo, Fanggeng Zou, Steven G. Younkin, Duane Beekly, Victoria Alvarez, Eliecer Coto, Cristina Razquin, Pau Pastor, Ignacio Mateo, Onofre Combarros, Kelley M. Faber, Tatiana M. Foroud, Hilkka Soininen, Mikko Hiltunen, Deborah Blacker, Thomas H. Mosley, Caroline Graff, Clive Holmes, Thomas J. Montine, Jerome I. Rotter, Alexis Brice, Michael A. Nalls, John S.K. Kauwe, Eric Boerwinkle, Reinhold Schmidt, Dan Rujescu, Christophe Tzourio, Markus M. Nöthen, Lenore J. Launer, Sudha Seshadri

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1794 Scopus citations

Abstract

Eleven susceptibility loci for lateonset 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, twostage metaanalysis of genomewide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform metaanalysis 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 genomewide significance (P < 5 × 10-8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1452-1458
Number of pages7
JournalNature genetics
Volume45
Issue number12
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Genetics

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    Lambert, J. C., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., Jun, G., DeStefano, A. L., Bis, J. C., Beecham, G. W., Grenier-Boley, B., Russo, G., Thornton-Wells, T. A., Jones, N., Smith, A. V., Chouraki, V., Thomas, C., Ikram, M. A., Zelenika, D., ... Seshadri, S. (2013). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature genetics, 45(12), 1452-1458. https://doi.org/10.1038/ng.2802