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 |
|---|---|
| Pages (from-to) | 429-436 |
| Number of pages | 8 |
| Journal | Nature Genetics |
| Volume | 43 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2011 |
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Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. / Hollingworth, Paul; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Lambert, Jean Charles; Carrasquillo, Minerva M.; Abraham, Richard; Hamshere, Marian L.; Pahwa, Jaspreet Singh; Moskvina, Valentina; Dowzell, Kimberley; Jones, Nicola; Stretton, Alexandra; Thomas, Charlene; Richards, Alex; Ivanov, Dobril; Widdowson, Caroline; Chapman, Jade; Lovestone, Simon; Powell, John; Proitsi, Petroula; Lupton, Michelle K.; Brayne, Carol; Rubinsztein, David C.; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Brown, Kristelle S.; Passmore, Peter A.; Craig, David; McGuinness, Bernadette; Todd, Stephen; Holmes, Clive; Mann, David; Smith, A. David; Beaumont, Helen; Warden, Donald; Wilcock, Gordon; Love, Seth; Kehoe, Patrick G.; Hooper, Nigel M.; Vardy, Emma R L C; Hardy, John; Mead, Simon; Fox, Nick C.; Rossor, Martin; Collinge, John; Maier, Wolfgang; Jessen, Frank; Rüther, Eckart; Schürmann, Britta; Heun, Reiner; Kölsch, Heike; Van Den Bussche, Hendrik; Heuser, Isabella; Kornhuber, Johannes; Wiltfang, Jens; Dichgans, Martin; Frölich, Lutz; Hampel, Harald; Gallacher, John; Hüll, Michael; Rujescu, Dan; Giegling, Ina; Goate, Alison M.; Kauwe, John S K; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin; Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine; Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew; Gwilliam, Rhian; Deloukas, Panagiotis; Al-Chalabi, Ammar; Shaw, Christopher E.; Tsolaki, Magda; Singleton, Andrew B.; Guerreiro, Rita; Mühleisen, Thomas W.; Nöthen, Markus M.; Moebus, Susanne; Jöckel, Karl Heinz; Klopp, Norman; Wichmann, H. Erich; Pankratz, V. Shane; Sando, Sigrid B.; Aasly, Jan O.; Barcikowska, Maria; Wszolek, Zbigniew K.; Dickson, Dennis W.; Graff-Radford, Neill R.; Petersen, Ronald C.; Van Duijn, Cornelia M.; Breteler, Monique M B; Ikram, M. Arfan; Destefano, Anita L.; Fitzpatrick, Annette L.; Lopez, Oscar; Launer, Lenore J.; Seshadri, Sudha; Berr, Claudine; Campion, Dominique; Epelbaum, Jacques; Dartigues, Jean François; Tzourio, Christophe; Alpérovitch, Annick; Lathrop, Mark; Feulner, Thomas M.; Friedrich, Patricia; Riehle, Caterina; Krawczak, Michael; Schreiber, Stefan; Mayhaus, Manuel; Nicolhaus, S.; Wagenpfeil, Stefan; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari; SnÆdal, Jon; Björnsson, Sigurbjörn; Jonsson, Palmi V.; Chouraki, Vincent; Genier-Boley, Benjamin; Hiltunen, Mikko; Soininen, Hilkka; Combarros, Onofre; Zelenika, Diana; Delepine, Marc; Bullido, Maria J.; Pasquier, Florence; Mateo, Ignacio; Frank-Garcia, Ana; Porcellini, Elisa; Hanon, Olivier; Coto, Eliecer; Alvarez, Victoria; Bosco, Paolo; Siciliano, Gabriele; Mancuso, Michelangelo; Panza, Francesco; Solfrizzi, Vincenzo; Nacmias, Benedetta; Sorbi, Sandro; 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, Peter A.; Jonsson, Thorlakur; Riemenschneider, Matthias; Morgan, Kevin; Younkin, Steven G.; Owen, Michael J.; O'Donovan, Michael; Amouyel, Philippe; Williams, Julie.
In: Nature Genetics, Vol. 43, No. 5, 05.2011, p. 429-436.Research output: Contribution to journal › Article
}
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).
UR - http://www.scopus.com/inward/record.url?scp=79955484414&partnerID=8YFLogxK
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
VL - 43
SP - 429
EP - 436
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -