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

We sought to identify new susceptibility loci for Alzheimer’s disease (AD) through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer’s Disease Genetic Consortium (ADGC). First, we undertook a combined analysis of four genome-wide association datasets (Stage...

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Detalles Bibliográficos
Autores principales: 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, Schürmann, Britta, Rüther, Eckart, Heun, Reiner, Kölsch, Heike, van den Bussche, Hendrik, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Gallacher, John, 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 MB, 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
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084173/
https://www.ncbi.nlm.nih.gov/pubmed/21460840
http://dx.doi.org/10.1038/ng.803
Descripción
Sumario:We sought to identify new susceptibility loci for Alzheimer’s disease (AD) through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer’s Disease Genetic Consortium (ADGC). First, we undertook a combined analysis of four genome-wide association datasets (Stage 1) and identified 10 novel variants with P≤1×10(−5). These were tested 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 provide compelling evidence that ABCA7 (meta-P 4.5×10(−17); including ADGC meta-P=5.0×10(−21)) and the MS4A gene cluster (rs610932, meta-P=1.8×10(−14); including ADGC meta-P=1.2×10(−16); rs670139, meta-P=1.4×10(−9); including ADGC meta-P=1.1×10(−10)) are novel susceptibility loci for AD. Second, we observed independent evidence for association for three suggestive loci reported by the ADGC GWAS, which when combined shows genome-wide significance: CD2AP (GERAD+ P=8.0×10(−4); including ADGC meta-P=8.6×10(−9)), CD33 (GERAD+ P=2.2×10(−4); including ADGC meta-P=1.6×10(−9)) and EPHA1 (GERAD+ P=3.4×10(−4); including ADGC meta-P=6.0×10(−10)). These findings support five novel susceptibility genes for AD.

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