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. Vardarajan; Yoichiro 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

doi:10.1038/ng.2802

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

2113 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 language	English (US)
Pages (from-to)	1452-1458
Number of pages	7
Journal	Nature Genetics
Volume	45
Issue number	12
DOIs	https://doi.org/10.1038/ng.2802
State	Published - Dec 1 2013

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.2802

Cite this

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

Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, Naj, AC, Sims, R, Bellenguez, C, Jun, G, DeStefano, AL, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Jones, N, Smith, AV, Chouraki, V, Thomas, C, Ikram, MA, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Gerrish, A, Schmidt, H, Kunkle, B, Fiévet, N, Amouyel, P, Pasquier, F, Deramecourt, V, De Bruijn, RFAG, Amin, N, Hofman, A, Van Duijn, CM, Dunstan, ML, Hollingworth, P, Owen, MJ, O'Donovan, MC, Jones, L, Holmans, PA, Moskvina, V, Williams, J, Baldwin, C, Farrer, LA, Choi, SH, Lunetta, KL, Fitzpatrick, AL, Harris, TB, Psaty, BM, Gilbert, JR, Hamilton-Nelson, KL, Martin, ER, Pericak-Vance, MA, Haines, JL, Gudnason, V, Jonsson, PV, Eiriksdottir, G, Bihoreau, MT, Lathrop, M, Valladares, O, Cantwell, LB, Wang, LS, Schellenberg, GD, Ruiz, A, Boada, M, Reitz, C, Mayeux, R, Ramirez, A, Maier, W, Hanon, O, Kukull, WA, Buxbaum, JD, Campion, D, Wallon, D, Hannequin, D, Crane, PK, Larson, EB, Becker, T, Cruchaga, C, Goate, AM, Craig, D, Johnston, JA, Mc-Guinness, B, Todd, S, Passmore, P, Berr, C, Ritchie, K, Lopez, OL, De Jager, PL, Evans, D, Lovestone, S, Proitsi, P, Powell, JF, Letenneur, L, Barberger-Gateau, P, Dufouil, C, Dartigues, JF, Morón, FJ, Rubinsztein, DC, St. George-Hyslop, P, Sleegers, K, Bettens, K, Van Broeckhoven, C, Huentelman, MJ, Gill, M, Brown, K, Morgan, K, Kamboh, MI, Keller, L, Fratiglioni, L, Green, R, Myers, AJ, Love, S, Rogaeva, E, Gallacher, J, Bayer, A, Clarimon, J, Lleo, A, Tsuang, DW, Yu, L, Bennett, DA, Tsolaki, M, Bossù, P, Spalletta, G, Collinge, J, Mead, S, Sorbi, S, Nacmias, B, Sanchez-Garcia, F, Deniz Naranjo, MC, Fox, NC, Hardy, J, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Mancuso, M, Matthews, F, Moebus, S, Mecocci, P, Del Zompo, M, Hampel, H, Pilotto, A, Bullido, M, Panza, F, Caffarra, P, Mayhaus, M, Pichler, S, Gu, W, Riemenschneider, M, Lannfelt, L, Ingelsson, M, Hakonarson, H, Carrasquillo, MM, Zou, F, Younkin, SG, Beekly, D, Alvarez, V, Coto, E, Razquin, C, Pastor, P, Mateo, I, Combarros, O, Faber, KM, Foroud, TM, Soininen, H, Hiltunen, M, Blacker, D, Mosley, TH, Graff, C, Holmes, C, Montine, TJ, Rotter, JI, Brice, A, Nalls, MA, Kauwe, JSK, Boerwinkle, E, Schmidt, R, Rujescu, D, Tzourio, C, Nöthen, MM, Launer, LJ & Seshadri, S 2013, 'Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease', Nature Genetics, vol. 45, no. 12, pp. 1452-1458. https://doi.org/10.1038/ng.2802

@article{92a1489dc9ee4012869be54cad8a8e59,

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

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.",

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

note = "Funding Information: This work was made possible by the generous participation of the control subjects, the patients and their families. iSelect chips were funded by the French National Foundation on Alzheimer{\textquoteright}s Disease and Related Disorders. Data management involved the Centre National de G{\'e}notypage and was supported by the Institut Pasteur de Lille, INSERM, FRC (Fondation pour la Recherche sur le Cerveau) and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer{\textquoteright}s Disease). The French National Foundation on Alzheimer{\textquoteright}s Disease and Related Disorders and the Alzheimer{\textquoteright}s Association (Chicago, Illinois) grant supported in-person meetings and communication for IGAP, and the Alzheimer{\textquoteright}s Association (Chicago, Illinois) grant provided some funds to each consortium for analyses. Funding Information: GERAD was supported by the Wellcome Trust, the MRC, Alzheimer{\textquoteright}s Research UK (ARUK) and the Welsh government. ADGC and CHARGE were supported by the US National Institutes of Health, National Institute on Aging (NIH-NIA), including grants U01 AG032984 and R01 AG033193 (additional US National Institutes of Health grant numbers are listed in the Supplementary Note). CHARGE was also supported by Erasmus Medical Center and Erasmus University. Complete acknowledgments are detailed in the Supplementary Note. Publisher Copyright: {\textcopyright} 2013 Macmillan Publishers Limited. All Rights Reserved.",

year = "2013",

month = dec,

day = "1",

doi = "10.1038/ng.2802",

language = "English (US)",

volume = "45",

pages = "1452--1458",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

T1 - Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

AU - Lambert, Jean Charles

AU - Ibrahim-Verbaas, Carla A.

AU - Harold, Denise

AU - Naj, Adam C.

AU - Sims, Rebecca

AU - Bellenguez, Céline

AU - Jun, Gyungah

AU - DeStefano, Anita L.

AU - Bis, Joshua C.

AU - Beecham, Gary W.

AU - Grenier-Boley, Benjamin

AU - Russo, Giancarlo

AU - Thornton-Wells, Tricia A.

AU - Jones, Nicola

AU - Smith, Albert V.

AU - Chouraki, Vincent

AU - Thomas, Charlene

AU - Ikram, M. Arfan

AU - Zelenika, Diana

AU - Vardarajan, Badri N.

AU - Kamatani, Yoichiro

AU - Lin, Chiao Feng

AU - Gerrish, Amy

AU - Schmidt, Helena

AU - Kunkle, Brian

AU - Fiévet, Nathalie

AU - Amouyel, Philippe

AU - Pasquier, Florence

AU - Deramecourt, Vincent

AU - De Bruijn, Renee F.A.G.

AU - Amin, Najaf

AU - Hofman, Albert

AU - Van Duijn, Cornelia M.

AU - Dunstan, Melanie L.

AU - Hollingworth, Paul

AU - Owen, Michael J.

AU - O'Donovan, Michael C.

AU - Jones, Lesley

AU - Holmans, Peter A.

AU - Moskvina, Valentina

AU - Williams, Julie

AU - Baldwin, Clinton

AU - Farrer, Lindsay A.

AU - Choi, Seung Hoan

AU - Lunetta, Kathryn L.

AU - Fitzpatrick, Annette L.

AU - Harris, Tamara B.

AU - Psaty, Bruce M.

AU - Gilbert, John R.

AU - Hamilton-Nelson, Kara L.

AU - Martin, Eden R.

AU - Pericak-Vance, Margaret A.

AU - Haines, Jonathan L.

AU - Gudnason, Vilmundur

AU - Jonsson, Palmi V.

AU - Eiriksdottir, Gudny

AU - Bihoreau, Marie Thérèse

AU - Lathrop, Mark

AU - Valladares, Otto

AU - Cantwell, Laura B.

AU - Wang, Li San

AU - Schellenberg, Gerard D.

AU - Ruiz, Agustin

AU - Boada, Mercè

AU - Reitz, Christiane

AU - Mayeux, Richard

AU - Ramirez, Alfredo

AU - Maier, Wolfgang

AU - Hanon, Olivier

AU - Kukull, Walter A.

AU - Buxbaum, Joseph D.

AU - Campion, Dominique

AU - Wallon, David

AU - Hannequin, Didier

AU - Crane, Paul K.

AU - Larson, Eric B.

AU - Becker, Tim

AU - Cruchaga, Carlos

AU - Goate, Alison M.

AU - Craig, David

AU - Johnston, Janet A.

AU - Mc-Guinness, Bernadette

AU - Todd, Stephen

AU - Passmore, Peter

AU - Berr, Claudine

AU - Ritchie, Karen

AU - Lopez, Oscar L.

AU - De Jager, Philip L.

AU - Evans, Denis

AU - Lovestone, Simon

AU - Proitsi, Petroula

AU - Powell, John F.

AU - Letenneur, Luc

AU - Barberger-Gateau, Pascale

AU - Dufouil, Carole

AU - Dartigues, Jean François

AU - Morón, Francisco J.

AU - Rubinsztein, David C.

AU - St. George-Hyslop, Peter

AU - Sleegers, Kristel

AU - Bettens, Karolien

AU - Van Broeckhoven, Christine

AU - Huentelman, Matthew J.

AU - Gill, Michael

AU - Brown, Kristelle

AU - Morgan, Kevin

AU - Kamboh, M. Ilyas

AU - Keller, Lina

AU - Fratiglioni, Laura

AU - Green, Robert

AU - Myers, Amanda J.

AU - Love, Seth

AU - Rogaeva, Ekaterina

AU - Gallacher, John

AU - Bayer, Anthony

AU - Clarimon, Jordi

AU - Lleo, Alberto

AU - Tsuang, Debby W.

AU - Yu, Lei

AU - Bennett, David A.

AU - Tsolaki, Magda

AU - Bossù, Paola

AU - Spalletta, Gianfranco

AU - Collinge, John

AU - Mead, Simon

AU - Sorbi, Sandro

AU - Nacmias, Benedetta

AU - Sanchez-Garcia, Florentino

AU - Deniz Naranjo, Maria Candida

AU - Fox, Nick C.

AU - Hardy, John

AU - Bosco, Paolo

AU - Clarke, Robert

AU - Brayne, Carol

AU - Galimberti, Daniela

AU - Mancuso, Michelangelo

AU - Matthews, Fiona

AU - Moebus, Susanne

AU - Mecocci, Patrizia

AU - Del Zompo, Maria

AU - Hampel, Harald

AU - Pilotto, Alberto

AU - Bullido, Maria

AU - Panza, Francesco

AU - Caffarra, Paolo

AU - Mayhaus, Manuel

AU - Pichler, Sabrina

AU - Gu, Wei

AU - Riemenschneider, Matthias

AU - Lannfelt, Lars

AU - Ingelsson, Martin

AU - Hakonarson, Hakon

AU - Carrasquillo, Minerva M.

AU - Zou, Fanggeng

AU - Younkin, Steven G.

AU - Beekly, Duane

AU - Alvarez, Victoria

AU - Coto, Eliecer

AU - Razquin, Cristina

AU - Pastor, Pau

AU - Mateo, Ignacio

AU - Combarros, Onofre

AU - Faber, Kelley M.

AU - Foroud, Tatiana M.

AU - Soininen, Hilkka

AU - Hiltunen, Mikko

AU - Blacker, Deborah

AU - Mosley, Thomas H.

AU - Graff, Caroline

AU - Holmes, Clive

AU - Montine, Thomas J.

AU - Rotter, Jerome I.

AU - Brice, Alexis

AU - Nalls, Michael A.

AU - Kauwe, John S.K.

AU - Boerwinkle, Eric

AU - Schmidt, Reinhold

AU - Rujescu, Dan

AU - Tzourio, Christophe

AU - Nöthen, Markus M.

AU - Launer, Lenore J.

AU - Seshadri, Sudha

N1 - Funding Information: This work was made possible by the generous participation of the control subjects, the patients and their families. iSelect chips were funded by the French National Foundation on Alzheimer’s Disease and Related Disorders. Data management involved the Centre National de Génotypage and was supported by the Institut Pasteur de Lille, INSERM, FRC (Fondation pour la Recherche sur le Cerveau) and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer’s Disease). The French National Foundation on Alzheimer’s Disease and Related Disorders and the Alzheimer’s Association (Chicago, Illinois) grant supported in-person meetings and communication for IGAP, and the Alzheimer’s Association (Chicago, Illinois) grant provided some funds to each consortium for analyses. Funding Information: GERAD was supported by the Wellcome Trust, the MRC, Alzheimer’s Research UK (ARUK) and the Welsh government. ADGC and CHARGE were supported by the US National Institutes of Health, National Institute on Aging (NIH-NIA), including grants U01 AG032984 and R01 AG033193 (additional US National Institutes of Health grant numbers are listed in the Supplementary Note). CHARGE was also supported by Erasmus Medical Center and Erasmus University. Complete acknowledgments are detailed in the Supplementary Note. Publisher Copyright: © 2013 Macmillan Publishers Limited. All Rights Reserved.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84888317489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888317489&partnerID=8YFLogxK

U2 - 10.1038/ng.2802

DO - 10.1038/ng.2802

M3 - Article

C2 - 24162737

AN - SCOPUS:84888317489

SN - 1061-4036

VL - 45

SP - 1452

EP - 1458

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this