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

Autoria(s): Hollingworth, P.; Harold, D.; Sims, R.; Gerrish, A.; Lambert, J.C.; Carrasquillo, M.M.; Abraham, R.; Hamshere, M.L.; Pahwa, J.S.; 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, M.K.; Brayne, C.; Rubinsztein, D.C.; Gill, M.; Lawlor, B.; Lynch, A.; Brown, K.S.; Passmore, Peter; Craig, David; McGuinness, Bernadette; Todd, Stephen; Holmes, C.; Mann, D.; Smith, A.D.; Beaumont, H.; Warden, D.; Wilcock, G.; Love, S.; Kehoe, P.G.; Hooper, N.M.; Vardy, E.R.L.C.; Hardy, J.; Mead, S.; Fox, N.C.; Rossor, M.; Collinge, J.; Maier, W.; Jessen, F.; Ruther, E.; Schurmann, B.; Heun, R.; Kolsch, H.; Van Den Bussche, H.; Heuser, I.; Kornhuber, J.; Wiltfang, J.; Dichgans, M.; Frolich, L.; Hampel, H.; Gallacher, J.; Hull, M.; Rujescu, D.; Giegling, I.; Goate, A.M.; Kauwe, J.S.K.; Cruchaga, C.; Nowotny, P.; Morris, J.C.; Mayo, K.; Sleegers, K.; Bettens, K.; Engelborghs, S.; De Deyn, P.P.; Van Broeckhoven, C.; Livingston, G.; Bass, N.J.; Gurling, H.; McQuillin, A.; Gwilliam, R.; Deloukas, P.; Al-Chalabi, A.; Shaw, C.E.; Tsolaki, M.; Singleton, A.B.; Guerreiro, R.; Muhleisen, T.W.; Nothen, M.M.; Moebus, S.; Jockel, K.H.; Klopp, N.; Wichmann, H.E.; Pankratz, V.S.; Sando, S.B.; Aasly, J.O.; Barcikowska, M.; Wszolek, Z.K.; Dickson, D.W.; Graff-Radford, N.R.; Petersen, R.C.; Van Duijn, C.M.; Breteler, M.M.B.; Ikram, M.A.; DeStefano, A.L.; Fitzpatrick, A.L.; Lopez, O.; Launer, L.J.; Seshadri, S.; Berr, C.; Campion, D.; Epelbaum, J.; Dartigues, J.F.; Tzourio, C.; Alperovitch, A.; Lathrop, M.; Feulner, T.M.; Friedrich, P.; Riehle, C.; Krawczak, M.; Schreiber, S.; Mayhaus, M.; Nicolhaus, S.; Wagenpfeil, S.; Steinberg, S.; Stefansson, H.; Stefansson, K.; Snaedal, J.; Bjornsson, S.; Jonsson, P.V.; Chouraki, V.; Genier-Boley, B.; Hiltunen, M.; Soininen, H.; Combarros, O.; Zelenika, D.; Delepine, M.; Bullido, M.J.; 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.; Bossu, P.; Piccardi, P.; Arosio, B.; Annoni, G.; Seripa, D.; Pilotto, A.; Scarpini, E.; Galimberti, D.; Brice, A.; Hannequin, D.; Licastro, F.; Jones, L.; Holmans, P.A.; Jonsson, T.; Riemenschneider, M.; Morgan, K.; Younkin, S.G.; Owen, M.J.; O'Donovan, M.; Amouyel, P.; Williams, J.
Data(s)

01/05/2011
Resumo

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)).
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application/pdf
Identificador

http://pure.qub.ac.uk/portal/en/publications/common-variants-at-abca7-ms4a6ams4a4e-epha1-cd33-and-cd2ap-are-associated-with-alzheimers-disease(b4e883ff-82db-4798-b8f2-4527ccb1b146).html

http://dx.doi.org/10.1038/ng.803

http://pure.qub.ac.uk/ws/files/6244690/Common_variants_at_ABCA7_MS4A6A_MS4A4E_EPHA1_CD33_and_CD2AP_are_associated_with_Alzheimer_s_disease.pdf
Idioma(s)

eng
Direitos

info:eu-repo/semantics/openAccess
Fonte

Hollingworth , P , Harold , D , Sims , R , Gerrish , A , Lambert , J C , Carrasquillo , M M , Abraham , R , Hamshere , M L , Pahwa , J S , 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 , M K , Brayne , C , Rubinsztein , D C , Gill , M , Lawlor , B , Lynch , A , Brown , K S , Passmore , P , Craig , D , McGuinness , B , Todd , S , Holmes , C , Mann , D , Smith , A D , Beaumont , H , Warden , D , Wilcock , G , Love , S , Kehoe , P G , Hooper , N M , Vardy , E R L C , Hardy , J , Mead , S , Fox , N C , Rossor , M , Collinge , J , Maier , W , Jessen , F , Ruther , E , Schurmann , B , Heun , R , Kolsch , H , Van Den Bussche , H , Heuser , I , Kornhuber , J , Wiltfang , J , Dichgans , M , Frolich , L , Hampel , H , Gallacher , J , Hull , M , Rujescu , D , Giegling , I , Goate , A M , Kauwe , J S K , Cruchaga , C , Nowotny , P , Morris , J C , Mayo , K , Sleegers , K , Bettens , K , Engelborghs , S , De Deyn , P P , Van Broeckhoven , C , Livingston , G , Bass , N J , Gurling , H , McQuillin , A , Gwilliam , R , Deloukas , P , Al-Chalabi , A , Shaw , C E , Tsolaki , M , Singleton , A B , Guerreiro , R , Muhleisen , T W , Nothen , M M , Moebus , S , Jockel , K H , Klopp , N , Wichmann , H E , Pankratz , V S , Sando , S B , Aasly , J O , Barcikowska , M , Wszolek , Z K , Dickson , D W , Graff-Radford , N R , Petersen , R C , Van Duijn , C M , Breteler , M M B , Ikram , M A , DeStefano , A L , Fitzpatrick , A L , Lopez , O , Launer , L J , Seshadri , S , Berr , C , Campion , D , Epelbaum , J , Dartigues , J F , Tzourio , C , Alperovitch , A , Lathrop , M , Feulner , T M , Friedrich , P , Riehle , C , Krawczak , M , Schreiber , S , Mayhaus , M , Nicolhaus , S , Wagenpfeil , S , Steinberg , S , Stefansson , H , Stefansson , K , Snaedal , J , Bjornsson , S , Jonsson , P V , Chouraki , V , Genier-Boley , B , Hiltunen , M , Soininen , H , Combarros , O , Zelenika , D , Delepine , M , Bullido , M J , 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 , Bossu , P , Piccardi , P , Arosio , B , Annoni , G , Seripa , D , Pilotto , A , Scarpini , E , Galimberti , D , Brice , A , Hannequin , D , Licastro , F , Jones , L , Holmans , P A , Jonsson , T , Riemenschneider , M , Morgan , K , Younkin , S G , Owen , M J , O'Donovan , M , Amouyel , P & Williams , J 2011 , ' Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease ' Nature Genetics , vol 43 , no. 5 , pp. 429-35 . DOI: 10.1038/ng.803
Palavras-Chave #/dk/atira/pure/subjectarea/asjc/1300/1311 #Genetics
Tipo

article
Acesso ao item digital