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

van Duijn, Cm; Wszolek, Zk K.; Younkin, Sg G.; Hollingworth, Paul; Carrasquillo, Minerva Mm; Tw, Mühleisen; Vs, Pankratz; Harold, Denise; Jones, Nicola; Hamshere, Ml L.; Stretton, Alexandra; Sims, Rebecca; Thomas, Charlene; Richards, Alex; Ivanov, Dobril; Lambert, Jc-C.; Pahwa, Js S.; Gerrish, Amy; Widdowson, Caroline; Chapman, Jade; Lovestone, Simon; Powell, John; Vardy, Er R. L. C.; Proitsi, Petroula; Mm, Carrasquillo; Brayne, Carol; Gill, Michael; Lupton, Mk K.; Lawlor, Brian; Lynch, Aoibhinn; Rubinsztein, Dc C.; van den Bussche, Hendrik; Abraham, Richard; Van Den Bussche, H.; Craig, David; Wiltfang, Jens; McGuinness, Bernadette; Todd, Stephen; Brown, Ks S.; Holmes, Clive; Mann, David; Passmore, Pa A.; Smith, Ad David; Beaumont, Helen; Warden, Donald; Wilcock, Gordon; Love, Seth; David Smith, A.; Ad, Smith; Moskvina, Valentina; Kehoe, Pg G.; Jc, Lambert; Hardy, John; Hooper, Nm M.; Mead, Simon; Dowzell, Kimberley; Fox, Nc C.; Rossor, Martin; Collinge, John; Maier, Wolfgang; Jessen, Frank; Rüther, Eckart; Schürmann, Britta; Heun, Reiner; Kölsch, Heike; Kolsch, Heike; Heuser, Isabella; Am, Goate; Kornhuber, Johannes; Dichgans, Martin; Frölich, Lutz; Hampel, Harald; Gallacher, John; Js, Kauwe; Hüll, Michael; Rujescu, Dan; Kauwe, Jsk S. K.; Giegling, Ina; Goate, Alison M.; Jc, Morris; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Pp, De Deyn; Mayo, Kevin; Sleegers, Kristel; Zelenika, Diana; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter Pp; Van Broeckhoven, Christine; Nj, Bass; Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew; Ce, Shaw; Gwilliam, Rhian; Deloukas, Panagiotis; Al-Chalabi, Ammar; Shaw, Christopher E.; Erich Wichmann, H.; Tsolaki, Magda; Singleton, Andrew B.; Guerreiro, Rita; Mühleisen, Thomas W.; Mm, Nöthen; Nöthen, Markus Mm; Moebus, Susanne; Shane Pankratz, V.; Klopp, Norman; Wichmann, He-Erich; Jöckel, Kh-H.; Pankratz, Vs Shane; Sando, Sigrid B.; Kh, Jöckel; Aasly, Jan O.; Barcikowska, Maria; He, Wichmann; Sb, Sando; Jo, Aasly; Nothen, Markus Mm; Dickson, Dw W.; Arfan Ikram, M.; Van Duijn, C. M.; Graff-Radford, Nr R.; Ikram, M. Arfan; DeStefano, Anita L.; Petersen, Rc C.; Jockel, Kh; Ml, Hamshere; Breteler, Mmb M. B.; Lopez, Oscar; Seshadri, Sudha; Berr, Claudine; Campion, Dominique; Epelbaum, Jacques; Destefano, Al L.; ALZHEIMER&amp;apos,; Tzourio, Christophe; Disease Neuroimaging Initiative, S.; Alpérovitch, Annick; Fitzpatrick, Al L.; Lathrop, Mark; Friedrich, Patricia; Launer, Lj J.; Riehle, Caterina; Krawczak, Michael; Js, Pahwa; Schreiber, Stefan; Mayhaus, Manuel; Mm, Breteler; Nicolhaus, S.; Wagenpfeil, Stefan; Steinberg, Stacy; Feulner, Tm M.; Stefansson, Hreinn; Stefansson, Kari; Dartigues, Jf-F.; Snaedal, Jon; Björnsson, Sigurbjorn; Consortium, Charge; Chouraki, Vincent; Jf, Dartigues; Genier-Boley, Benjamin; Hiltunen, Mikko; Soininen, Hilkka; Combarros, Onofre; Initiative, Alzheimer's Disease Neuroimaging; Jonsson, Pv; Delepine, Marc; Consortium, Eadi; Pasquier, Florence; Mateo, Ignacio; Frank-Garcia, Ana; Porcellini, Elisa; Bullido, Mj J.; Hanon, Olivier; Coto, Eliecer; Alvarez, Victoria; Bosco, Paolo; Siciliano, Gabriele; Mancuso, Michelangelo; Panza, Francesco; Solfrizzi, Vincenzo; Nacmias, Benedetta; Sorbi, Sandro; Eadi1, Consortium; Bossù, Paola; Piccardi, Paola; Arosio, Beatrice; Annoni, Giorgio; Seripa, Davide; Pilotto, Alberto; Scarpini, Elio; Galimberti, Daniela; Brice, Alexis; Hannequin, Didier; Licastro, Federico; Jones, Lesley; Holmans, Pa A.; Owen, Mj J.; Jonsson, Thorlakur; Riemenschneider, Matthias; Morgan, Kevin; O&amp;apos,; Neuroimaging, Alzheimer's Dis; Broeckhoven, Van Christine; O'Donovan, Michael; Amouyel, Philippe; Donovan, M.; Williams, Julie; Others,

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van Duijn et al., 2011

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@article{van Duijn2011,
  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). © 2011 Nature America, Inc. All rights reserved.},
  author = {van Duijn, Cm and Wszolek, Zk K. and Younkin, Sg G. and Hollingworth, Paul and Carrasquillo, Minerva Mm and Tw, Mühleisen and Vs, Pankratz and Harold, Denise and Jones, Nicola and Hamshere, Ml L. and Stretton, Alexandra and Sims, Rebecca and Thomas, Charlene and Richards, Alex and Ivanov, Dobril and Lambert, Jc-C. and Pahwa, Js S. and Gerrish, Amy and Widdowson, Caroline and Chapman, Jade and Lovestone, Simon and Powell, John and Vardy, Er R. L. C. and Proitsi, Petroula and Mm, Carrasquillo and Brayne, Carol and Gill, Michael and Lupton, Mk K. and Lawlor, Brian and Lynch, Aoibhinn and Rubinsztein, Dc C. and van den Bussche, Hendrik and Abraham, Richard and Van Den Bussche, H. and Craig, David and Wiltfang, Jens and McGuinness, Bernadette and Todd, Stephen and Brown, Ks S. and Holmes, Clive and Mann, David and Passmore, Pa A. and Smith, Ad David and Beaumont, Helen and Warden, Donald and Wilcock, Gordon and Love, Seth and David Smith, A. and Ad, Smith and Moskvina, Valentina and Kehoe, Pg G. and Jc, Lambert and Hardy, John and Hooper, Nm M. and Mead, Simon and Dowzell, Kimberley and Fox, Nc C. and Rossor, Martin and Collinge, John and Maier, Wolfgang and Jessen, Frank and Rüther, Eckart and Schürmann, Britta and Heun, Reiner and Kölsch, Heike and Kolsch, Heike and Heuser, Isabella and Am, Goate and Kornhuber, Johannes and Dichgans, Martin and Frölich, Lutz and Hampel, Harald and Gallacher, John and Js, Kauwe and Hüll, Michael and Rujescu, Dan and Kauwe, Jsk S. K. and Giegling, Ina and Goate, Alison M. and Jc, Morris and Cruchaga, Carlos and Nowotny, Petra and Morris, John C. and Pp, De Deyn and Mayo, Kevin and Sleegers, Kristel and Zelenika, Diana and Bettens, Karolien and Engelborghs, Sebastiaan and De Deyn, Peter Pp and Van Broeckhoven, Christine and Nj, Bass and Livingston, Gill and Bass, Nicholas J. and Gurling, Hugh and McQuillin, Andrew and Ce, Shaw and Gwilliam, Rhian and Deloukas, Panagiotis and Al-Chalabi, Ammar and Shaw, Christopher E. and Erich Wichmann, H. and Tsolaki, Magda and Singleton, Andrew B. and Guerreiro, Rita and Mühleisen, Thomas W. and Mm, Nöthen and Nöthen, Markus Mm and Moebus, Susanne and Shane Pankratz, V. and Klopp, Norman and Wichmann, He-Erich and Jöckel, Kh-H. and Pankratz, Vs Shane and Sando, Sigrid B. and Kh, Jöckel and Aasly, Jan O. and Barcikowska, Maria and He, Wichmann and Sb, Sando and Jo, Aasly and Nothen, Markus Mm and Dickson, Dw W. and Arfan Ikram, M. and Van Duijn, C. M. and Graff-Radford, Nr R. and Ikram, M. Arfan and DeStefano, Anita L. and Petersen, Rc C. and Jockel, Kh and Ml, Hamshere and Breteler, Mmb M. B. and Lopez, Oscar and Seshadri, Sudha and Berr, Claudine and Campion, Dominique and Epelbaum, Jacques and Destefano, Al L. and ALZHEIMER&amp;apos,  and Tzourio, Christophe and Disease Neuroimaging Initiative, S. and Alpérovitch, Annick and Fitzpatrick, Al L. and Lathrop, Mark and Friedrich, Patricia and Launer, Lj J. and Riehle, Caterina and Krawczak, Michael and Js, Pahwa and Schreiber, Stefan and Mayhaus, Manuel and Mm, Breteler and Nicolhaus, S. and Wagenpfeil, Stefan and Steinberg, Stacy and Feulner, Tm M. and Stefansson, Hreinn and Stefansson, Kari and Dartigues, Jf-F. and Snaedal, Jon and Björnsson, Sigurbjorn and Consortium, Charge and Chouraki, Vincent and Jf, Dartigues and Genier-Boley, Benjamin and Hiltunen, Mikko and Soininen, Hilkka and Combarros, Onofre and Initiative, Alzheimer's Disease Neuroimaging and Jonsson, Pv and Delepine, Marc and Consortium, Eadi and Pasquier, Florence and Mateo, Ignacio and Frank-Garcia, Ana and Porcellini, Elisa and Bullido, Mj J. and Hanon, Olivier and Coto, Eliecer and Alvarez, Victoria and Bosco, Paolo and Siciliano, Gabriele and Mancuso, Michelangelo and Panza, Francesco and Solfrizzi, Vincenzo and Nacmias, Benedetta and Sorbi, Sandro and Eadi1, Consortium and Bossù, Paola and Piccardi, Paola and Arosio, Beatrice and Annoni, Giorgio and Seripa, Davide and Pilotto, Alberto and Scarpini, Elio and Galimberti, Daniela and Brice, Alexis and Hannequin, Didier and Licastro, Federico and Jones, Lesley and Holmans, Pa A. and Owen, Mj J. and Jonsson, Thorlakur and Riemenschneider, Matthias and Morgan, Kevin and O&amp;apos,  and Neuroimaging, Alzheimer's Dis and Broeckhoven, Van Christine and O'Donovan, Michael and Amouyel, Philippe and Donovan, M. and Williams, Julie and Others, },
  doi = {10.1038/ng.803},
  month = {apr},
  title = {Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.},
  url = {http://www.nature.com/articles/ng.803.pdf},
  year = {2011}
}

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

Journal article published in 2011 by Cm van Duijn, Zk K. Wszolek, Sg G. Younkin, Paul Hollingworth, Minerva Mm Carrasquillo, Mühleisen Tw, Pankratz Vs, Denise Harold, Nicola Jones, Ml L. Hamshere, Alexandra Stretton, Rebecca Sims, Charlene Thomas, Alex Richards, Dobril Ivanov

and other authors. Cm van Duijn, Zk K. Wszolek, Sg G. Younkin, Paul Hollingworth, Minerva Mm Carrasquillo, Mühleisen Tw, Pankratz Vs, Denise Harold, Nicola Jones, Ml L. Hamshere, Alexandra Stretton, Rebecca Sims, Charlene Thomas, Alex Richards, Dobril Ivanov

, Jc-C. Lambert, Js S. Pahwa, Amy Gerrish, Caroline Widdowson, Jade Chapman, Simon Lovestone, John Powell, Er R. L. C. Vardy, Petroula Proitsi, Carrasquillo Mm, Carol Brayne, Michael Gill, Mk K. Lupton, Brian Lawlor, Aoibhinn Lynch, Dc C. Rubinsztein, Hendrik van den Bussche, Richard Abraham, H. Van Den Bussche, David Craig, Jens Wiltfang, Bernadette McGuinness, Stephen Todd, Ks S. Brown, Clive Holmes, David Mann, Pa A. Passmore, Ad David Smith, Helen Beaumont, Donald Warden, Gordon Wilcock, Seth Love, A. David Smith, Smith Ad, Valentina Moskvina, Pg G. Kehoe, Lambert Jc, John Hardy, Nm M. Hooper, Simon Mead, Kimberley Dowzell, Nc C. Fox

, Martin Rossor, John Collinge, Wolfgang Maier, Frank Jessen, Eckart Rüther, Britta Schürmann, Reiner Heun, Heike Kölsch, Heike Kolsch, Isabella Heuser, Goate Am, Johannes Kornhuber

, Martin Dichgans, Lutz Frölich, Harald Hampel, John Gallacher, Kauwe Js, Michael Hüll, Dan Rujescu, Jsk S. K. Kauwe, Ina Giegling, Alison M. Goate, Morris Jc, Carlos Cruchaga, Petra Nowotny, John C. Morris, De Deyn Pp, Kevin Mayo, Kristel Sleegers, Diana Zelenika, Karolien Bettens, Sebastiaan Engelborghs, Peter Pp De Deyn, Christine Van Broeckhoven, Bass Nj, Gill Livingston

, Nicholas J. Bass, Hugh Gurling, Andrew McQuillin, Shaw Ce, Rhian Gwilliam, Panagiotis Deloukas

, Ammar Al-Chalabi

, Christopher E. Shaw, H. Erich Wichmann, Magda Tsolaki, Andrew B. Singleton, Rita Guerreiro, Thomas W. Mühleisen, Nöthen Mm, Markus Mm Nöthen, Susanne Moebus, V. Shane Pankratz, Norman Klopp, He-Erich Wichmann, Kh-H. Jöckel, Vs Shane Pankratz, Sigrid B. Sando, Jöckel Kh, Jan O. Aasly, Maria Barcikowska, Wichmann He, Sando Sb, Aasly Jo, Markus Mm Nothen, Dw W. Dickson, M. Arfan Ikram, C. M. Van Duijn, Nr R. Graff-Radford, M. Arfan Ikram

, Anita L. DeStefano, Rc C. Petersen, Kh Jockel, Hamshere Ml, Mmb M. B. Breteler, Oscar Lopez, Sudha Seshadri, Claudine Berr, Dominique Campion, Jacques Epelbaum, Al L. Destefano, ALZHEIMER&apos, Christophe Tzourio

, S. Disease Neuroimaging Initiative, Annick Alpérovitch, Al L. Fitzpatrick, Mark Lathrop, Patricia Friedrich, Lj J. Launer, Caterina Riehle, Michael Krawczak, Pahwa Js, Stefan Schreiber, Manuel Mayhaus, Breteler Mm, S. Nicolhaus, Stefan Wagenpfeil, Stacy Steinberg, Tm M. Feulner, Hreinn Stefansson, Kari Stefansson, Jf-F. Dartigues, Jon Snaedal, Sigurbjorn Björnsson, Charge Consortium, Vincent Chouraki

, Dartigues Jf, Benjamin Genier-Boley, Mikko Hiltunen, Hilkka Soininen, Onofre Combarros, Alzheimer's Disease Neuroimaging Initiative, Pv Jonsson, Marc Delepine, Eadi Consortium, Florence Pasquier, Ignacio Mateo, Ana Frank-Garcia, Elisa Porcellini, Mj J. Bullido, Olivier Hanon, Eliecer Coto, Victoria Alvarez, Paolo Bosco, Gabriele Siciliano, Michelangelo Mancuso, Francesco Panza, Vincenzo Solfrizzi, Benedetta Nacmias, Sandro Sorbi, Consortium Eadi1, Paola Bossù, Paola Piccardi, Beatrice Arosio, Giorgio Annoni, Davide Seripa, Alberto Pilotto, Elio Scarpini, Daniela Galimberti, Alexis Brice, Didier Hannequin, Federico Licastro, Lesley Jones, Pa A. Holmans, Mj J. Owen, Thorlakur Jonsson, Matthias Riemenschneider, Kevin Morgan, O&apos, Alzheimer's Dis Neuroimaging, Van Christine Broeckhoven, Michael O'Donovan

, Philippe Amouyel, M. Donovan, Julie Williams, Others

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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). © 2011 Nature America, Inc. All rights reserved.

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

Abstract