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- Title
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
- Authors
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; Snaedal, 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; Alzheimer's Disease Neuroimaging Initiative; CHARGE consortium; EADI1 consortium
- 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)).
- Publication
Nature genetics, 2011, Vol 43, Issue 5, p429
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.803