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Nature Genetics

Publication date: 2013-12-01
Volume: 45 Pages: 1452 - U206
Publisher: Nature Research

Author:

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

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, COMMON VARIANTS, GENETIC RISK, RECEPTOR, CD33, IMPUTATION, MUTATIONS, GENOTYPES, SEQUENCE, NEURONS, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Case-Control Studies, Cohort Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, European Alzheimer's Disease Initiative (EADI), Genetic and Environmental Risk in Alzheimer's Disease, Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

Abstract:

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.