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

Hollingworth, Paul, Harold, Denise ORCID: https://orcid.org/0000-0001-5195-0143, Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, Gerrish, Amy, Lambert, Jean-Charles, Carrasquillo, Minerva M., Abraham, Richard Alun, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Pahwa, Jaspreet Singh, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Dowzell, Kimberley Frances, Denning, Nicola, Stretton, Alexandra, Thomas, Charlene, Richards, Alexander, Ivanov, Dobril ORCID: https://orcid.org/0000-0001-6271-6301, Widdowson, Caroline Susan, Chapman, Jade Alice, 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 Edward ORCID: https://orcid.org/0000-0002-2394-5299, 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 ORCID: https://orcid.org/0000-0002-3007-4612, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Jonsson, Thorlakur, Riemenschneider, Matthias, Morgan, Kevin, Younkin, Steven G., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Amouyel, Philippe and Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 2011. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genetics 43 (5) , pp. 429-435. 10.1038/ng.803

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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 ≤ 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).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Nature Publishing Group
ISSN:	1061-4036
Last Modified:	05 Jan 2024 04:42
URI:	https://orca.cardiff.ac.uk/id/eprint/30228

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