title: Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.
abstract: 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 x 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 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.
authors.affiliation: Inserm U744, Lille, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Simon
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authors.forename: Gael
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authors.forename: Béatrice
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authors.forename: Karolien
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authors.forename: Claudine
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authors.forename: Florence
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authors.forename: Sebastiaan
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authors.forename: Ana
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authors.forename: Elisa
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authors.forename: Olivier
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authors.initials: MM
authors.lastname: de Pancorbo
authors.forename: Corinne
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authors.lastname: Dufouil
authors.forename: Céline
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authors.lastname: Jaillard
authors.forename: Thierry
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authors.lastname: Leveillard
authors.forename: Victoria
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authors.lastname: Alvarez
authors.forename: Paolo
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authors.lastname: Bosco
authors.forename: Michelangelo
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authors.lastname: Mancuso
authors.forename: Francesco
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authors.lastname: Panza
authors.forename: Benedetta
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authors.lastname: Nacmias
authors.forename: Paola
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authors.lastname: Bossù
authors.forename: Paola
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authors.lastname: Piccardi
authors.forename: Giorgio
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authors.lastname: Annoni
authors.forename: Davide
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authors.lastname: Seripa
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.forename: Federico
authors.initials: F
authors.lastname: Licastro
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.forename: Hélène
authors.initials: H
authors.lastname: Blanché
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.forename: Christophe
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authors.lastname: Tzourio
authors.forename: Ivo
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authors.lastname: Gut
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Annick
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authors.lastname: Alpérovitch
authors.forename: Mark
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authors.lastname: Lathrop
authors.forename: Philippe
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authors.lastname: Amouyel
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D051152:Clusterin / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017463:Receptors, Complement 3b / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D017463:Receptors, Complement 3b