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

P. Hollingworth; D. Harold; R. Sims; A. Gerrish; J.C. Lambert; M.M. Carrasquillo; R. Abraham; M.L. Hamshere; J.S. Pahwa; V. Moskvina; K. Dowzell; N. Jones; A. Stretton; C. Thomas; A. Richards; D. Ivanov; C. Widdowson; J. Chapman; S. Lovestone; J. Powell; P. Proitsi; M.K. Lupton; C. Brayne; D.C. Rubinsztein; M. Gill; B. Lawlor; A. Lynch; K.S. Brown; Peter Passmore; David Craig; Bernadette McGuinness; Stephen Todd; C. Holmes; D. Mann; A.D. Smith; H. Beaumont; D. Warden; G. Wilcock; S. Love; P.G. Kehoe; N.M. Hooper; E.R.L.C. Vardy; J. Hardy; S. Mead; N.C. Fox; M. Rossor; J. Collinge; W. Maier; F. Jessen; E. Ruther; B. Schurmann; R. Heun; H. Kolsch; H. Van Den Bussche; I. Heuser; J. Kornhuber; J. Wiltfang; M. Dichgans; L. Frolich; H. Hampel; J. Gallacher; M. Hull; D. Rujescu; I. Giegling; A.M. Goate; J.S.K. Kauwe; C. Cruchaga; P. Nowotny; J.C. Morris; K. Mayo; K. Sleegers; K. Bettens; S. Engelborghs; P.P. De Deyn; C. Van Broeckhoven; G. Livingston; N.J. Bass; H. Gurling; A. McQuillin; R. Gwilliam; P. Deloukas; A. Al-Chalabi; C.E. Shaw; M. Tsolaki; A.B. Singleton; R. Guerreiro; T.W. Muhleisen; M.M. Nothen; S. Moebus; K.H. Jockel; N. Klopp; H.E. Wichmann; V.S. Pankratz; S.B. Sando; J.O. Aasly; M. Barcikowska; Z.K. Wszolek; D.W. Dickson; N.R. Graff-Radford; R.C. Petersen; C.M. Van Duijn; M.M.B. Breteler; M.A. Ikram; A.L. DeStefano; A.L. Fitzpatrick; O. Lopez; L.J. Launer; S. Seshadri; C. Berr; D. Campion; J. Epelbaum; J.F. Dartigues; C. Tzourio; A. Alperovitch; M. Lathrop; T.M. Feulner; P. Friedrich; C. Riehle; M. Krawczak; S. Schreiber; M. Mayhaus; S. Nicolhaus; S. Wagenpfeil; S. Steinberg; H. Stefansson; K. Stefansson; J. Snaedal; S. Bjornsson; P.V. Jonsson; V. Chouraki; B. Genier-Boley; M. Hiltunen; H. Soininen; O. Combarros; D. Zelenika; M. Delepine; M.J. Bullido; F. Pasquier; I. Mateo; A. Frank-Garcia; E. Porcellini; O. Hanon; E. Coto; V. Alvarez; P. Bosco; G. Siciliano; M. Mancuso; F. Panza; V. Solfrizzi; B. Nacmias; S. Sorbi; P. Bossu; P. Piccardi; B. Arosio; G. Annoni; D. Seripa; A. Pilotto; E. Scarpini; D. Galimberti; A. Brice; D. Hannequin; F. Licastro; L. Jones; P.A. Holmans; T. Jonsson; M. Riemenschneider; K. Morgan; S.G. Younkin; M.J. Owen; M. O'Donovan; P. Amouyel; J. Williams

doi:10.1038/ng.803

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

P. Hollingworth
, D. Harold
, R. Sims
, A. Gerrish
, J.C. Lambert
, M.M. Carrasquillo
, R. Abraham
, M.L. Hamshere
, J.S. Pahwa
, V. Moskvina
, K. Dowzell
, N. Jones
, A. Stretton
, C. Thomas
, A. Richards
, D. Ivanov
, C. Widdowson
, J. Chapman
, S. Lovestone
, J. Powell

P. Proitsi, M.K. Lupton, C. Brayne, D.C. Rubinsztein, M. Gill, B. Lawlor, A. Lynch, K.S. Brown, Peter Passmore, David Craig, Bernadette McGuinness, Stephen Todd, C. Holmes, D. Mann, A.D. Smith, H. Beaumont, D. Warden, G. Wilcock, S. Love, P.G. Kehoe, N.M. Hooper, E.R.L.C. Vardy, J. Hardy, S. Mead, N.C. Fox, M. Rossor, J. Collinge, W. Maier, F. Jessen, E. Ruther, B. Schurmann, R. Heun, H. Kolsch, H. Van Den Bussche, I. Heuser, J. Kornhuber, J. Wiltfang, M. Dichgans, L. Frolich, H. Hampel, J. Gallacher, M. Hull, D. Rujescu, I. Giegling, A.M. Goate, J.S.K. Kauwe, C. Cruchaga, P. Nowotny, J.C. Morris, K. Mayo, K. Sleegers, K. Bettens, S. Engelborghs, P.P. De Deyn, C. Van Broeckhoven, G. Livingston, N.J. Bass, H. Gurling, A. McQuillin, R. Gwilliam, P. Deloukas, A. Al-Chalabi, C.E. Shaw, M. Tsolaki, A.B. Singleton, R. Guerreiro, T.W. Muhleisen, M.M. Nothen, S. Moebus, K.H. Jockel, N. Klopp, H.E. Wichmann, V.S. Pankratz, S.B. Sando, J.O. Aasly, M. Barcikowska, Z.K. Wszolek, D.W. Dickson, N.R. Graff-Radford, R.C. Petersen, C.M. Van Duijn, M.M.B. Breteler, M.A. Ikram, A.L. DeStefano, A.L. Fitzpatrick, O. Lopez, L.J. Launer, S. Seshadri, C. Berr, D. Campion, J. Epelbaum, J.F. Dartigues, C. Tzourio, A. Alperovitch, M. Lathrop, T.M. Feulner, P. Friedrich, C. Riehle, M. Krawczak, S. Schreiber, M. Mayhaus, S. Nicolhaus, S. Wagenpfeil, S. Steinberg, H. Stefansson, K. Stefansson, J. Snaedal, S. Bjornsson, P.V. Jonsson, V. Chouraki, B. Genier-Boley, M. Hiltunen, H. Soininen, O. Combarros, D. Zelenika, M. Delepine, M.J. Bullido, F. Pasquier, I. Mateo, A. Frank-Garcia, E. Porcellini, O. Hanon, E. Coto, V. Alvarez, P. Bosco, G. Siciliano, M. Mancuso, F. Panza, V. Solfrizzi, B. Nacmias, S. Sorbi, P. Bossu, P. Piccardi, B. Arosio, G. Annoni, D. Seripa, A. Pilotto, E. Scarpini, D. Galimberti, A. Brice, D. Hannequin, F. Licastro, L. Jones, P.A. Holmans, T. Jonsson, M. Riemenschneider, K. Morgan, S.G. Younkin, M.J. Owen, M. O'Donovan, P. Amouyel, J. Williams

School of Medicine, Dentistry and Biomedical Sciences

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

1758 Citations (Scopus)

472 Downloads (Pure)

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 = 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
Pages (from-to)	429-35
Journal	Nature Genetics
Volume	43
Issue number	5
Early online date	03 Apr 2011
DOIs	https://doi.org/10.1038/ng.803
Publication status	Published - 01 May 2011

ASJC Scopus subject areas

Genetics

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Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
Copyright 2011 Nature America. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
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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), 429-35. https://doi.org/10.1038/ng.803

@article{b4e883ff82db4798b8f24527ccb1b146,

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 = 1 {\texttimes} 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 {\texttimes} 10(-17); including ADGC data, meta P = 5.0 {\texttimes} 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 {\texttimes} 10(-14); including ADGC data, meta P = 1.2 {\texttimes} 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 {\texttimes} 10(-4); including ADGC data, meta P = 8.6 {\texttimes} 10(-9)), CD33 (GERAD+, P = 2.2 {\texttimes} 10(-4); including ADGC data, meta P = 1.6 {\texttimes} 10(-9)) and EPHA1 (GERAD+, P = 3.4 {\texttimes} 10(-4); including ADGC data, meta P = 6.0 {\texttimes} 10(-10)). ",

author = "P. Hollingworth and D. Harold and R. Sims and A. Gerrish and J.C. Lambert and M.M. Carrasquillo and R. Abraham and M.L. Hamshere and J.S. Pahwa and V. Moskvina and K. Dowzell and N. Jones and A. Stretton and C. Thomas and A. Richards and D. Ivanov and C. Widdowson and J. Chapman and S. Lovestone and J. Powell and P. Proitsi and M.K. Lupton and C. Brayne and D.C. Rubinsztein and M. Gill and B. Lawlor and A. Lynch and K.S. Brown and Peter Passmore and David Craig and Bernadette McGuinness and Stephen Todd and C. Holmes and D. Mann and A.D. Smith and H. Beaumont and D. Warden and G. Wilcock and S. Love and P.G. Kehoe and N.M. Hooper and E.R.L.C. Vardy and J. Hardy and S. Mead and N.C. Fox and M. Rossor and J. Collinge and W. Maier and F. Jessen and E. Ruther and B. Schurmann and R. Heun and H. Kolsch and \{Van Den Bussche\}, H. and I. Heuser and J. Kornhuber and J. Wiltfang and M. Dichgans and L. Frolich and H. Hampel and J. Gallacher and M. Hull and D. Rujescu and I. Giegling and A.M. Goate and J.S.K. Kauwe and C. Cruchaga and P. Nowotny and J.C. Morris and K. Mayo and K. Sleegers and K. Bettens and S. Engelborghs and \{De Deyn\}, P.P. and \{Van Broeckhoven\}, C. and G. Livingston and N.J. Bass and H. Gurling and A. McQuillin and R. Gwilliam and P. Deloukas and A. Al-Chalabi and C.E. Shaw and M. Tsolaki and A.B. Singleton and R. Guerreiro and T.W. Muhleisen and M.M. Nothen and S. Moebus and K.H. Jockel and N. Klopp and H.E. Wichmann and V.S. Pankratz and S.B. Sando and J.O. Aasly and M. Barcikowska and Z.K. Wszolek and D.W. Dickson and N.R. Graff-Radford and R.C. Petersen and \{Van Duijn\}, C.M. and M.M.B. Breteler and M.A. Ikram and A.L. DeStefano and A.L. Fitzpatrick and O. Lopez and L.J. Launer and S. Seshadri and C. Berr and D. Campion and J. Epelbaum and J.F. Dartigues and C. Tzourio and A. Alperovitch and M. Lathrop and T.M. Feulner and P. Friedrich and C. Riehle and M. Krawczak and S. Schreiber and M. Mayhaus and S. Nicolhaus and S. Wagenpfeil and S. Steinberg and H. Stefansson and K. Stefansson and J. Snaedal and S. Bjornsson and P.V. Jonsson and V. Chouraki and B. Genier-Boley and M. Hiltunen and H. Soininen and O. Combarros and D. Zelenika and M. Delepine and M.J. Bullido and F. Pasquier and I. Mateo and A. Frank-Garcia and E. Porcellini and O. Hanon and E. Coto and V. Alvarez and P. Bosco and G. Siciliano and M. Mancuso and F. Panza and V. Solfrizzi and B. Nacmias and S. Sorbi and P. Bossu and P. Piccardi and B. Arosio and G. Annoni and D. Seripa and A. Pilotto and E. Scarpini and D. Galimberti and A. Brice and D. Hannequin and F. Licastro and L. Jones and P.A. Holmans and T. Jonsson and M. Riemenschneider and K. Morgan and S.G. Younkin and M.J. Owen and M. O'Donovan and P. Amouyel and J. Williams",

year = "2011",

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doi = "10.1038/ng.803",

language = "English",

volume = "43",

pages = "429--35",

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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, P, 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, Ruther, E, Schurmann, B, Heun, R, Kolsch, H, Van Den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frolich, L, Hampel, H, Gallacher, J, Hull, 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, Muhleisen, TW, Nothen, MM, Moebus, S, Jockel, 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, Alperovitch, 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, Snaedal, J, Bjornsson, 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, Bossu, 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. 429-35. https://doi.org/10.1038/ng.803

TY - JOUR

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

AU - Hollingworth, P.

AU - Harold, D.

AU - Sims, R.

AU - Gerrish, A.

AU - Lambert, J.C.

AU - Carrasquillo, M.M.

AU - Abraham, R.

AU - Hamshere, M.L.

AU - Pahwa, J.S.

AU - Moskvina, V.

AU - Dowzell, K.

AU - Jones, N.

AU - Stretton, A.

AU - Thomas, C.

AU - Richards, A.

AU - Ivanov, D.

AU - Widdowson, C.

AU - Chapman, J.

AU - Lovestone, S.

AU - Powell, J.

AU - Proitsi, P.

AU - Lupton, M.K.

AU - Brayne, C.

AU - Rubinsztein, D.C.

AU - Gill, M.

AU - Lawlor, B.

AU - Lynch, A.

AU - Brown, K.S.

AU - Passmore, Peter

AU - Craig, David

AU - McGuinness, Bernadette

AU - Todd, Stephen

AU - Holmes, C.

AU - Mann, D.

AU - Smith, A.D.

AU - Beaumont, H.

AU - Warden, D.

AU - Wilcock, G.

AU - Love, S.

AU - Kehoe, P.G.

AU - Hooper, N.M.

AU - Vardy, E.R.L.C.

AU - Hardy, J.

AU - Mead, S.

AU - Fox, N.C.

AU - Rossor, M.

AU - Collinge, J.

AU - Maier, W.

AU - Jessen, F.

AU - Ruther, E.

AU - Schurmann, B.

AU - Heun, R.

AU - Kolsch, H.

AU - Van Den Bussche, H.

AU - Heuser, I.

AU - Kornhuber, J.

AU - Wiltfang, J.

AU - Dichgans, M.

AU - Frolich, L.

AU - Hampel, H.

AU - Gallacher, J.

AU - Hull, M.

AU - Rujescu, D.

AU - Giegling, I.

AU - Goate, A.M.

AU - Kauwe, J.S.K.

AU - Cruchaga, C.

AU - Nowotny, P.

AU - Morris, J.C.

AU - Mayo, K.

AU - Sleegers, K.

AU - Bettens, K.

AU - Engelborghs, S.

AU - De Deyn, P.P.

AU - Van Broeckhoven, C.

AU - Livingston, G.

AU - Bass, N.J.

AU - Gurling, H.

AU - McQuillin, A.

AU - Gwilliam, R.

AU - Deloukas, P.

AU - Al-Chalabi, A.

AU - Shaw, C.E.

AU - Tsolaki, M.

AU - Singleton, A.B.

AU - Guerreiro, R.

AU - Muhleisen, T.W.

AU - Nothen, M.M.

AU - Moebus, S.

AU - Jockel, K.H.

AU - Klopp, N.

AU - Wichmann, H.E.

AU - Pankratz, V.S.

AU - Sando, S.B.

AU - Aasly, J.O.

AU - Barcikowska, M.

AU - Wszolek, Z.K.

AU - Dickson, D.W.

AU - Graff-Radford, N.R.

AU - Petersen, R.C.

AU - Van Duijn, C.M.

AU - Breteler, M.M.B.

AU - Ikram, M.A.

AU - DeStefano, A.L.

AU - Fitzpatrick, A.L.

AU - Lopez, O.

AU - Launer, L.J.

AU - Seshadri, S.

AU - Berr, C.

AU - Campion, D.

AU - Epelbaum, J.

AU - Dartigues, J.F.

AU - Tzourio, C.

AU - Alperovitch, A.

AU - Lathrop, M.

AU - Feulner, T.M.

AU - Friedrich, P.

AU - Riehle, C.

AU - Krawczak, M.

AU - Schreiber, S.

AU - Mayhaus, M.

AU - Nicolhaus, S.

AU - Wagenpfeil, S.

AU - Steinberg, S.

AU - Stefansson, H.

AU - Stefansson, K.

AU - Snaedal, J.

AU - Bjornsson, S.

AU - Jonsson, P.V.

AU - Chouraki, V.

AU - Genier-Boley, B.

AU - Hiltunen, M.

AU - Soininen, H.

AU - Combarros, O.

AU - Zelenika, D.

AU - Delepine, M.

AU - Bullido, M.J.

AU - Pasquier, F.

AU - Mateo, I.

AU - Frank-Garcia, A.

AU - Porcellini, E.

AU - Hanon, O.

AU - Coto, E.

AU - Alvarez, V.

AU - Bosco, P.

AU - Siciliano, G.

AU - Mancuso, M.

AU - Panza, F.

AU - Solfrizzi, V.

AU - Nacmias, B.

AU - Sorbi, S.

AU - Bossu, P.

AU - Piccardi, P.

AU - Arosio, B.

AU - Annoni, G.

AU - Seripa, D.

AU - Pilotto, A.

AU - Scarpini, E.

AU - Galimberti, D.

AU - Brice, A.

AU - Hannequin, D.

AU - Licastro, F.

AU - Jones, L.

AU - Holmans, P.A.

AU - Jonsson, T.

AU - Riemenschneider, M.

AU - Morgan, K.

AU - Younkin, S.G.

AU - Owen, M.J.

AU - O'Donovan, M.

AU - Amouyel, P.

AU - Williams, J.

PY - 2011/5/1

Y1 - 2011/5/1

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 = 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 = 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)).

U2 - 10.1038/ng.803

DO - 10.1038/ng.803

M3 - Article

C2 - 21460840

SN - 1061-4036

VL - 43

SP - 429

EP - 435

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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