title: Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations.
abstract: Recent genome-wide association studies have identified 5 loci (BIN1, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [CI] [1.15-1.38], p = 2.9 × 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 × 10(-7), respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% CI [1.06-1.32], p = 2.0 × 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation.
authors.affiliation: INSERM U744, Lille, France. jean-charles.lambert@pasteur-lille.fr
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Diana
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authors.lastname: Zelenika
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authors.lastname: Hiltunen
authors.forename: Vincent
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authors.forename: Onofre
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authors.forename: Nathalie
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authors.lastname: Fiévet
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authors.forename: Eliecer
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authors.forename: Ignacio
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authors.forename: Seppo
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authors.lastname: Porcellini
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authors.forename: Paola
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authors.forename: Raffaele
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authors.lastname: Ferri
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authors.forename: Elio
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authors.lastname: Scarpini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Vincenzo
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authors.lastname: Solfrizzi
authors.forename: Sandro
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authors.lastname: Sorbi
authors.forename: Gianfranco
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authors.lastname: Spalletta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ravaglia
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
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
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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: Federico
authors.initials: F
authors.lastname: Licastro
authors.forename: Mark
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authors.lastname: Lathrop
authors.forename: Hilkka
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authors.lastname: Soininen
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics*; D005387:Finland; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D025521:Tumor Suppressor Proteins