The University of Southampton
University of Southampton Institutional Repository

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

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for 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.
1061-4036
1452-1458
Lambert, Jean-Charles
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Holmes, Clive
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Amouyel, Philippe
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Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A, Harold, Denise, Naj, Adam C, Sims, Rebecca, Bellenguez, Céline, 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-Thérèse, 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, Morón, Francisco J, Rubinsztein, David C, Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M, Fiévet, 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, Bossù, 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 F A G, 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 S K, Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Mercè, Hiltunen, Mikko, Martin, Eden R, Schmidt, Reinhold, Rujescu, Dan, Wang, Li-San, Dartigues, Jean-François, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Nöthen, 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 and Amouyel, Philippe (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature Genetics, 45 (12), 1452-1458. (doi:10.1038/ng.2802).

Record type: Article

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.

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Published date: 2013
Organisations: Faculty of Medicine

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Local EPrints ID: 369403
URI: http://eprints.soton.ac.uk/id/eprint/369403
ISSN: 1061-4036
PURE UUID: c30cd624-5b3f-4200-a498-43f14ab7c99f
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

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Date deposited: 25 Sep 2014 12:09
Last modified: 18 Feb 2021 16:53

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Contributors

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

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