Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
Title | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J-C, Carrasquillo, MM, Abraham, R, Hamshere, ML, Pahwa, JSingh, 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, PA, Craig, D, McGuinness, B, Todd, S, Holmes, C, Mann, D, A Smith, D, 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, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, 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, Mühleisen, TW, Nöthen, MM, Moebus, S, Jöckel, K-H, Klopp, N, Wichmann, H-E, V Pankratz, S, Sando, SB, Aasly, JO, Barcikowska, M, Wszolek, ZK, Dickson, DW, Graff-Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, M Ikram, A, DeStefano, AL, Fitzpatrick, AL, Lopez, O, Launer, LJ, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J-F, Tzourio, C, Alpérovitch, 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, Björnsson, 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, Bossù, 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 |
Corporate Authors | Alzheimer's Disease Neuroimaging Initiative, CHARGE consortium, EADI1 consortium |
Journal | Nat Genet |
Volume | 43 |
Issue | 5 |
Pagination | 429-35 |
Date Published | 2011 May |
ISSN | 1546-1718 |
Keywords | Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Alzheimer Disease, Antigens, CD, Antigens, Differentiation, Myelomonocytic, ATP-Binding Cassette Transporters, Case-Control Studies, Cytoskeletal Proteins, Databases, Genetic, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Multigene Family, Polymorphism, Single Nucleotide, Receptor, EphA1, Sialic Acid Binding Ig-like Lectin 3 |
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)). |
DOI | 10.1038/ng.803 |
Alternate Journal | Nat. Genet. |
PubMed ID | 21460840 |
PubMed Central ID | PMC3084173 |
Grant List | G0801306 / / Medical Research Council / United Kingdom U24 AG021886 / AG / NIA NIH HHS / United States G0802189 / / Medical Research Council / United Kingdom MC_U123160651 / / Medical Research Council / United Kingdom G0701075 / / Medical Research Council / United Kingdom U19 AG010483 / AG / NIA NIH HHS / United States / / Medical Research Council / United Kingdom G0300429 / / Medical Research Council / United Kingdom 082604 / / Wellcome Trust / United Kingdom G0902227 / / Medical Research Council / United Kingdom G0900688 / / Medical Research Council / United Kingdom G0601846 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom G9810900 / / Medical Research Council / United Kingdom MC_G1000734 / / Medical Research Council / United Kingdom |