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Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's diseaseJaillard, Céline; Bettens, Karolien; Alpérovitch, Annick; Van Broeckhoven, Christine; Ritchie, Karen; Mancuso, Michelangelo; Fiévet, Nathalie; Annoni, Giorgio; Galimberti, Daniela; Alvarez, Victoria; Tzourio, Christophe; Gut, Ivo; Leveillard, Thierry; Licastro, Federico; Zelenika, Diana; Panza, Francesco; Soininen, Hilkka; Barberger-Gateau, Pascale; Pasquier, Florence; Lendon, Corinne; De Deyn, Peter; Bullido, Maria J; Hiltunen, Mikko; Dufouil, Carole; Piccardi, Paola; Lambert, Jean-Charles; Seripa, Davide; Blanché, Hélène; Dartigues, Jean-François; Nacmias, Benedetta; de Pancorbo, Marian M; Lathrop, Mark; Hannequin, Didier; Franck, Ana; Heath, Simon; Hanon, Olivier; Tavernier, Béatrice; Bosco, Paolo; Porcellini, Elisa; Letenneur, Luc; Engelborghs, Sebastiaan; Even, Gael; Berr, Claudine; Amouyel, Philippe; Campion, Dominique; Mateo, Ignacio; Combarros, Onofre; Helisalmi, Seppo; Sleegers, Kristel; Bossù, Paola
Nature genetics, 10/2009, Volume: 41, Issue: 10Journal Article
The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P < 10−5) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 × 10−9 for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 × 10−9 for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of β amyloid (Aβ) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.
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