Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Paul Hollingworth; Denise Harold; Rebecca Sims; Amy Gerrish; Jean Charles Lambert; Minerva M. Carrasquillo; Richard Abraham; Marian L. Hamshere; Jaspreet Singh Pahwa; Valentina Moskvina; Kimberley Dowzell; Nicola Jones; Alexandra Stretton; Charlene Thomas; Alex Richards; Dobril Ivanov; Caroline Widdowson; Jade Chapman; Simon Lovestone; John Powell; Petroula Proitsi; Michelle K. Lupton; Carol Brayne; David C. Rubinsztein; Michael Gill; Brian Lawlor; Aoibhinn Lynch; Kristelle S. Brown; Peter A. Passmore; David Craig; Bernadette McGuinness; Stephen Todd; Clive Holmes; David Mann; A. David Smith; Helen Beaumont; Donald Warden; Gordon Wilcock; Seth Love; Patrick G. Kehoe; Nigel M. Hooper; Emma R.L.C. Vardy; John Hardy; Simon Mead; Nick C. Fox; Martin Rossor; John Collinge; Wolfgang Maier; Frank Jessen; Eckart Rüther; Britta Schürmann; Reiner Heun; Heike Kölsch; Hendrik Van Den Bussche; Isabella Heuser; Johannes Kornhuber; Jens Wiltfang; Martin Dichgans; Lutz Frölich; Harald Hampel; John Gallacher; Michael Hüll; Dan Rujescu; Ina Giegling; Alison M. Goate; John S.K. Kauwe; Carlos Cruchaga; Petra Nowotny; John C. Morris; Kevin Mayo; Kristel Sleegers; Karolien Bettens; Sebastiaan Engelborghs; Peter P. De Deyn; Christine Van Broeckhoven; Gill Livingston; Nicholas J. Bass; Hugh Gurling; Andrew McQuillin; Rhian Gwilliam; Panagiotis Deloukas; Ammar Al-Chalabi; Christopher E. Shaw; Magda Tsolaki; Andrew B. Singleton; Rita Guerreiro; Thomas W. Mühleisen; Markus M. Nöthen; Susanne Moebus; Karl Heinz Jöckel; Norman Klopp; H. Erich Wichmann; V. Shane Pankratz; Sigrid B. Sando; Jan O. Aasly; Maria Barcikowska; Zbigniew K. Wszolek; Dennis W. Dickson; Neill R. Graff-Radford; Ronald C. Petersen; Cornelia M. Van Duijn; Monique M.B. Breteler; M. Arfan Ikram; Anita L. Destefano; Annette L. Fitzpatrick; Oscar Lopez; Lenore J. Launer; Sudha Seshadri; Claudine Berr; Dominique Campion; Jacques Epelbaum; Jean François Dartigues; Christophe Tzourio; Annick Alpérovitch; Mark Lathrop; Thomas M. Feulner; Patricia Friedrich; Caterina Riehle; Michael Krawczak; Stefan Schreiber; Manuel Mayhaus; S. Nicolhaus; Stefan Wagenpfeil; Stacy Steinberg; Hreinn Stefansson; Kari Stefansson; Jon SnÆdal; Sigurbjörn Björnsson; Palmi V. Jonsson; Vincent Chouraki; Benjamin Genier-Boley; Mikko Hiltunen; Hilkka Soininen; Onofre Combarros; Diana Zelenika; Marc Delepine; Maria J. Bullido; Florence Pasquier; Ignacio Mateo; Ana Frank-Garcia; Elisa Porcellini; Olivier Hanon; Eliecer Coto; Victoria Alvarez; Paolo Bosco; Gabriele Siciliano; Michelangelo Mancuso; Francesco Panza; Vincenzo Solfrizzi; Benedetta Nacmias; Sandro Sorbi; Paola Bossù; Paola Piccardi; Beatrice Arosio; Giorgio Annoni; Davide Seripa; Alberto Pilotto; Elio Scarpini; Daniela Galimberti; Alexis Brice; Didier Hannequin; Federico Licastro; Lesley Jones; Peter A. Holmans; Thorlakur Jonsson; Matthias Riemenschneider; Kevin Morgan; Steven G. Younkin; Michael J. Owen; Michael O'Donovan; Philippe Amouyel; Julie Williams

doi:10.1038/ng.803

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Paul Hollingworth, Denise Harold, Rebecca Sims, Amy Gerrish, Jean Charles Lambert, Minerva M. Carrasquillo, Richard Abraham, Marian L. Hamshere, Jaspreet Singh Pahwa, Valentina Moskvina, Kimberley Dowzell, Nicola Jones, Alexandra Stretton, Charlene Thomas, Alex Richards, Dobril Ivanov, Caroline Widdowson, Jade Chapman, Simon Lovestone, John PowellPetroula Proitsi, Michelle K. Lupton, Carol Brayne, David C. Rubinsztein, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Kristelle S. Brown, Peter A. Passmore, David Craig, Bernadette McGuinness, Stephen Todd, Clive Holmes, David Mann, A. David Smith, Helen Beaumont, Donald Warden, Gordon Wilcock, Seth Love, Patrick G. Kehoe, Nigel M. Hooper, Emma R.L.C. Vardy, John Hardy, Simon Mead, Nick C. Fox, Martin Rossor, John Collinge, Wolfgang Maier, Frank Jessen, Eckart Rüther, Britta Schürmann, Reiner Heun, Heike Kölsch, Hendrik Van Den Bussche, Isabella Heuser, Johannes Kornhuber, Jens Wiltfang, Martin Dichgans, Lutz Frölich, Harald Hampel, John Gallacher, Michael Hüll, Dan Rujescu, Ina Giegling, Alison M. Goate, John S.K. Kauwe, Carlos Cruchaga, Petra Nowotny, John C. Morris, Kevin Mayo, Kristel Sleegers, Karolien Bettens, Sebastiaan Engelborghs, Peter P. De Deyn, Christine Van Broeckhoven, Gill Livingston, Nicholas J. Bass, Hugh Gurling, Andrew McQuillin, Rhian Gwilliam, Panagiotis Deloukas, Ammar Al-Chalabi, Christopher E. Shaw, Magda Tsolaki, Andrew B. Singleton, Rita Guerreiro, Thomas W. Mühleisen, Markus M. Nöthen, Susanne Moebus, Karl Heinz Jöckel, Norman Klopp, H. Erich Wichmann, V. Shane Pankratz, Sigrid B. Sando, Jan O. Aasly, Maria Barcikowska, Zbigniew K. Wszolek, Dennis W. Dickson, Neill R. Graff-Radford, Ronald C. Petersen, Cornelia M. Van Duijn, Monique M.B. Breteler, M. Arfan Ikram, Anita L. Destefano, Annette L. Fitzpatrick, Oscar Lopez, Lenore J. Launer, Sudha Seshadri, Claudine Berr, Dominique Campion, Jacques Epelbaum, Jean François Dartigues, Christophe Tzourio, Annick Alpérovitch, Mark Lathrop, Thomas M. Feulner, Patricia Friedrich, Caterina Riehle, Michael Krawczak, Stefan Schreiber, Manuel Mayhaus, S. Nicolhaus, Stefan Wagenpfeil, Stacy Steinberg, Hreinn Stefansson, Kari Stefansson, Jon SnÆdal, Sigurbjörn Björnsson, Palmi V. Jonsson, Vincent Chouraki, Benjamin Genier-Boley, Mikko Hiltunen, Hilkka Soininen, Onofre Combarros, Diana Zelenika, Marc Delepine, Maria J. Bullido, Florence Pasquier, Ignacio Mateo, Ana Frank-Garcia, Elisa Porcellini, Olivier Hanon, Eliecer Coto, Victoria Alvarez, Paolo Bosco, Gabriele Siciliano, Michelangelo Mancuso, Francesco Panza, Vincenzo Solfrizzi, Benedetta Nacmias, Sandro Sorbi, Paola Bossù, Paola Piccardi, Beatrice Arosio, Giorgio Annoni, Davide Seripa, Alberto Pilotto, Elio Scarpini, Daniela Galimberti, Alexis Brice, Didier Hannequin, Federico Licastro, Lesley Jones, Peter A. Holmans, Thorlakur Jonsson, Matthias Riemenschneider, Kevin Morgan, Steven G. Younkin, Michael J. Owen, Michael O'Donovan, Philippe Amouyel, Julie Williams

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

1267 Scopus citations

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 ^-5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 ^-17; including ADGC data, meta P = 5.0 × 10 ^-21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 ^-14; including ADGC data, meta P = 1.2 × 10 ^-16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 ^-4; including ADGC data, meta P = 8.6 × 10 ^-9), CD33 (GERAD+, P = 2.2 × 10 ^-4; including ADGC data, meta P = 1.6 × 10 ^-9) and EPHA1 (GERAD+, P = 3.4 × 10 ^-4; including ADGC data, meta P = 6.0 × 10 ^-10).

Original language	English (US)
Pages (from-to)	429-436
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	5
DOIs	https://doi.org/10.1038/ng.803
State	Published - May 2011

ASJC Scopus subject areas

Genetics

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10.1038/ng.803

Cite this

Hollingworth, P., Harold, D., Sims, R., Gerrish, A., Lambert, J. C., Carrasquillo, M. M., Abraham, R., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Jones, N., Stretton, A., Thomas, C., Richards, A., Ivanov, D., Widdowson, C., Chapman, J., Lovestone, S., ... Williams, J. (2011). Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genetics, 43(5), 429-436. https://doi.org/10.1038/ng.803

Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, JC, Carrasquillo, MM, Abraham, R, Hamshere, ML, Pahwa, JS, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, MK, Brayne, C, Rubinsztein, DC, Gill, M, Lawlor, B, Lynch, A, Brown, KS, Passmore, PA, Craig, D, McGuinness, B, Todd, S, Holmes, C, Mann, D, Smith, AD, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, PG, Hooper, NM, Vardy, ERLC, Hardy, J, Mead, S, Fox, NC, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, Van Den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, AM, Kauwe, JSK, Cruchaga, C, Nowotny, P, Morris, JC, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, PP, Van Broeckhoven, C, Livingston, G, Bass, NJ, Gurling, H, McQuillin, A, Gwilliam, R, Deloukas, P, Al-Chalabi, A, Shaw, CE, Tsolaki, M, Singleton, AB, Guerreiro, R, Mühleisen, TW, Nöthen, MM, Moebus, S, Jöckel, KH, Klopp, N, Wichmann, HE, Pankratz, VS, Sando, SB, Aasly, JO, Barcikowska, M, Wszolek, ZK , Dickson, DW , Graff-Radford, NR , Petersen, RC, Van Duijn, CM, Breteler, MMB, Ikram, MA, Destefano, AL, Fitzpatrick, AL, Lopez, O, Launer, LJ, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, JF, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, TM, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, SnÆdal, J, Björnsson, S, Jonsson, PV, Chouraki, V, Genier-Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, MJ, Pasquier, F, Mateo, I, Frank-Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, PA, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, SG, Owen, MJ, O'Donovan, M, Amouyel, P & Williams, J 2011, 'Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease', Nature Genetics, vol. 43, no. 5, pp. 429-436. https://doi.org/10.1038/ng.803

@article{0749bf1aa59242218da693543a9da9b0,

title = "Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease",

abstract = "We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10).",

author = "Paul Hollingworth and Denise Harold and Rebecca Sims and Amy Gerrish and Lambert, {Jean Charles} and Carrasquillo, {Minerva M.} and Richard Abraham and Hamshere, {Marian L.} and Pahwa, {Jaspreet Singh} and Valentina Moskvina and Kimberley Dowzell and Nicola Jones and Alexandra Stretton and Charlene Thomas and Alex Richards and Dobril Ivanov and Caroline Widdowson and Jade Chapman and Simon Lovestone and John Powell and Petroula Proitsi and Lupton, {Michelle K.} and Carol Brayne and Rubinsztein, {David C.} and Michael Gill and Brian Lawlor and Aoibhinn Lynch and Brown, {Kristelle S.} and Passmore, {Peter A.} and David Craig and Bernadette McGuinness and Stephen Todd and Clive Holmes and David Mann and Smith, {A. David} and Helen Beaumont and Donald Warden and Gordon Wilcock and Seth Love and Kehoe, {Patrick G.} and Hooper, {Nigel M.} and Vardy, {Emma R.L.C.} and John Hardy and Simon Mead and Fox, {Nick C.} and Martin Rossor and John Collinge and Wolfgang Maier and Frank Jessen and Eckart R{\"u}ther and Britta Sch{\"u}rmann and Reiner Heun and Heike K{\"o}lsch and {Van Den Bussche}, Hendrik and Isabella Heuser and Johannes Kornhuber and Jens Wiltfang and Martin Dichgans and Lutz Fr{\"o}lich and Harald Hampel and John Gallacher and Michael H{\"u}ll and Dan Rujescu and Ina Giegling and Goate, {Alison M.} and Kauwe, {John S.K.} and Carlos Cruchaga and Petra Nowotny and Morris, {John C.} and Kevin Mayo and Kristel Sleegers and Karolien Bettens and Sebastiaan Engelborghs and {De Deyn}, {Peter P.} and {Van Broeckhoven}, Christine and Gill Livingston and Bass, {Nicholas J.} and Hugh Gurling and Andrew McQuillin and Rhian Gwilliam and Panagiotis Deloukas and Ammar Al-Chalabi and Shaw, {Christopher E.} and Magda Tsolaki and Singleton, {Andrew B.} and Rita Guerreiro and M{\"u}hleisen, {Thomas W.} and N{\"o}then, {Markus M.} and Susanne Moebus and J{\"o}ckel, {Karl Heinz} and Norman Klopp and Wichmann, {H. Erich} and Pankratz, {V. Shane} and Sando, {Sigrid B.} and Aasly, {Jan O.} and Maria Barcikowska and Wszolek, {Zbigniew K.} and Dickson, {Dennis W.} and Graff-Radford, {Neill R.} and Petersen, {Ronald C.} and {Van Duijn}, {Cornelia M.} and Breteler, {Monique M.B.} and Ikram, {M. Arfan} and Destefano, {Anita L.} and Fitzpatrick, {Annette L.} and Oscar Lopez and Launer, {Lenore J.} and Sudha Seshadri and Claudine Berr and Dominique Campion and Jacques Epelbaum and Dartigues, {Jean Fran{\c c}ois} and Christophe Tzourio and Annick Alp{\'e}rovitch and Mark Lathrop and Feulner, {Thomas M.} and Patricia Friedrich and Caterina Riehle and Michael Krawczak and Stefan Schreiber and Manuel Mayhaus and S. Nicolhaus and Stefan Wagenpfeil and Stacy Steinberg and Hreinn Stefansson and Kari Stefansson and Jon Sn{\AE}dal and Sigurbj{\"o}rn Bj{\"o}rnsson and Jonsson, {Palmi V.} and Vincent Chouraki and Benjamin Genier-Boley and Mikko Hiltunen and Hilkka Soininen and Onofre Combarros and Diana Zelenika and Marc Delepine and Bullido, {Maria J.} and Florence Pasquier and Ignacio Mateo and Ana Frank-Garcia and Elisa Porcellini and Olivier Hanon and Eliecer Coto and Victoria Alvarez and Paolo Bosco and Gabriele Siciliano and Michelangelo Mancuso and Francesco Panza and Vincenzo Solfrizzi and Benedetta Nacmias and Sandro Sorbi and Paola Boss{\`u} and Paola Piccardi and Beatrice Arosio and Giorgio Annoni and Davide Seripa and Alberto Pilotto and Elio Scarpini and Daniela Galimberti and Alexis Brice and Didier Hannequin and Federico Licastro and Lesley Jones and Holmans, {Peter A.} and Thorlakur Jonsson and Matthias Riemenschneider and Kevin Morgan and Younkin, {Steven G.} and Owen, {Michael J.} and Michael O'Donovan and Philippe Amouyel and Julie Williams",

year = "2011",

month = may,

doi = "10.1038/ng.803",

language = "English (US)",

volume = "43",

pages = "429--436",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

AU - Hollingworth, Paul

AU - Harold, Denise

AU - Sims, Rebecca

AU - Gerrish, Amy

AU - Lambert, Jean Charles

AU - Carrasquillo, Minerva M.

AU - Abraham, Richard

AU - Hamshere, Marian L.

AU - Pahwa, Jaspreet Singh

AU - Moskvina, Valentina

AU - Dowzell, Kimberley

AU - Jones, Nicola

AU - Stretton, Alexandra

AU - Thomas, Charlene

AU - Richards, Alex

AU - Ivanov, Dobril

AU - Widdowson, Caroline

AU - Chapman, Jade

AU - Lovestone, Simon

AU - Powell, John

AU - Proitsi, Petroula

AU - Lupton, Michelle K.

AU - Brayne, Carol

AU - Rubinsztein, David C.

AU - Gill, Michael

AU - Lawlor, Brian

AU - Lynch, Aoibhinn

AU - Brown, Kristelle S.

AU - Passmore, Peter A.

AU - Craig, David

AU - McGuinness, Bernadette

AU - Todd, Stephen

AU - Holmes, Clive

AU - Mann, David

AU - Smith, A. David

AU - Beaumont, Helen

AU - Warden, Donald

AU - Wilcock, Gordon

AU - Love, Seth

AU - Kehoe, Patrick G.

AU - Hooper, Nigel M.

AU - Vardy, Emma R.L.C.

AU - Hardy, John

AU - Mead, Simon

AU - Fox, Nick C.

AU - Rossor, Martin

AU - Collinge, John

AU - Maier, Wolfgang

AU - Jessen, Frank

AU - Rüther, Eckart

AU - Schürmann, Britta

AU - Heun, Reiner

AU - Kölsch, Heike

AU - Van Den Bussche, Hendrik

AU - Heuser, Isabella

AU - Kornhuber, Johannes

AU - Wiltfang, Jens

AU - Dichgans, Martin

AU - Frölich, Lutz

AU - Hampel, Harald

AU - Gallacher, John

AU - Hüll, Michael

AU - Rujescu, Dan

AU - Giegling, Ina

AU - Goate, Alison M.

AU - Kauwe, John S.K.

AU - Cruchaga, Carlos

AU - Nowotny, Petra

AU - Morris, John C.

AU - Mayo, Kevin

AU - Sleegers, Kristel

AU - Bettens, Karolien

AU - Engelborghs, Sebastiaan

AU - De Deyn, Peter P.

AU - Van Broeckhoven, Christine

AU - Livingston, Gill

AU - Bass, Nicholas J.

AU - Gurling, Hugh

AU - McQuillin, Andrew

AU - Gwilliam, Rhian

AU - Deloukas, Panagiotis

AU - Al-Chalabi, Ammar

AU - Shaw, Christopher E.

AU - Tsolaki, Magda

AU - Singleton, Andrew B.

AU - Guerreiro, Rita

AU - Mühleisen, Thomas W.

AU - Nöthen, Markus M.

AU - Moebus, Susanne

AU - Jöckel, Karl Heinz

AU - Klopp, Norman

AU - Wichmann, H. Erich

AU - Pankratz, V. Shane

AU - Sando, Sigrid B.

AU - Aasly, Jan O.

AU - Barcikowska, Maria

AU - Wszolek, Zbigniew K.

AU - Dickson, Dennis W.

AU - Graff-Radford, Neill R.

AU - Petersen, Ronald C.

AU - Van Duijn, Cornelia M.

AU - Breteler, Monique M.B.

AU - Ikram, M. Arfan

AU - Destefano, Anita L.

AU - Fitzpatrick, Annette L.

AU - Lopez, Oscar

AU - Launer, Lenore J.

AU - Seshadri, Sudha

AU - Berr, Claudine

AU - Campion, Dominique

AU - Epelbaum, Jacques

AU - Dartigues, Jean François

AU - Tzourio, Christophe

AU - Alpérovitch, Annick

AU - Lathrop, Mark

AU - Feulner, Thomas M.

AU - Friedrich, Patricia

AU - Riehle, Caterina

AU - Krawczak, Michael

AU - Schreiber, Stefan

AU - Mayhaus, Manuel

AU - Nicolhaus, S.

AU - Wagenpfeil, Stefan

AU - Steinberg, Stacy

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - SnÆdal, Jon

AU - Björnsson, Sigurbjörn

AU - Jonsson, Palmi V.

AU - Chouraki, Vincent

AU - Genier-Boley, Benjamin

AU - Hiltunen, Mikko

AU - Soininen, Hilkka

AU - Combarros, Onofre

AU - Zelenika, Diana

AU - Delepine, Marc

AU - Bullido, Maria J.

AU - Pasquier, Florence

AU - Mateo, Ignacio

AU - Frank-Garcia, Ana

AU - Porcellini, Elisa

AU - Hanon, Olivier

AU - Coto, Eliecer

AU - Alvarez, Victoria

AU - Bosco, Paolo

AU - Siciliano, Gabriele

AU - Mancuso, Michelangelo

AU - Panza, Francesco

AU - Solfrizzi, Vincenzo

AU - Nacmias, Benedetta

AU - Sorbi, Sandro

AU - Bossù, Paola

AU - Piccardi, Paola

AU - Arosio, Beatrice

AU - Annoni, Giorgio

AU - Seripa, Davide

AU - Pilotto, Alberto

AU - Scarpini, Elio

AU - Galimberti, Daniela

AU - Brice, Alexis

AU - Hannequin, Didier

AU - Licastro, Federico

AU - Jones, Lesley

AU - Holmans, Peter A.

AU - Jonsson, Thorlakur

AU - Riemenschneider, Matthias

AU - Morgan, Kevin

AU - Younkin, Steven G.

AU - Owen, Michael J.

AU - O'Donovan, Michael

AU - Amouyel, Philippe

AU - Williams, Julie

PY - 2011/5

Y1 - 2011/5

N2 - We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10).

AB - We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10).

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UR - http://www.scopus.com/inward/citedby.url?scp=79955484414&partnerID=8YFLogxK

U2 - 10.1038/ng.803

DO - 10.1038/ng.803

M3 - Article

C2 - 21460840

AN - SCOPUS:79955484414

SN - 1061-4036

VL - 43

SP - 429

EP - 436

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

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