Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Jean Charles Lambert; Diana Zelenika; Mikko Hiltunen; Vincent Chouraki; Onofre Combarros; Maria J. Bullido; Gloria Tognoni; Nathalie Fiévet; Anne Boland; Beatrice Arosio; Eliecer Coto; Maria Del Zompo; Ignacio Mateo; Ana Frank-Garcia; Seppo Helisalmi; Elisa Porcellini; Alberto Pilotto; Paola Forti; Raffaele Ferri; Marc Delepine; Elio Scarpini; Gabriele Siciliano; Vincenzo Solfrizzi; Sandro Sorbi; Gianfranco Spalletta; Giovanni Ravaglia; Fernando Valdivieso; Victoria Alvarez; Paolo Bosco; Michelangelo Mancuso; Francesco Panza; Benedetta Nacmias; Paola Bossu; Paola Piccardi; Giorgio Annoni; Davide Seripa; Daniela Galimberti; Federico Licastro; Mark Lathrop; Hilkka Soininen; Philippe Amouyel

doi:10.1016/j.neurobiolaging.2010.11.022

Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Jean Charles Lambert, Diana Zelenika, Mikko Hiltunen, Vincent Chouraki, Onofre Combarros, Maria J. Bullido, Gloria Tognoni, Nathalie Fiévet, Anne Boland, Beatrice Arosio, Eliecer Coto, Maria Del Zompo, Ignacio Mateo, Ana Frank-Garcia, Seppo Helisalmi, Elisa Porcellini, Alberto Pilotto, Paola Forti, Raffaele Ferri, Marc DelepineElio Scarpini, Gabriele Siciliano, Vincenzo Solfrizzi, Sandro Sorbi, Gianfranco Spalletta, Giovanni Ravaglia, Fernando Valdivieso, Victoria Alvarez, Paolo Bosco, Michelangelo Mancuso, Francesco Panza, Benedetta Nacmias, Paola Bossu, Paola Piccardi, Giorgio Annoni, Davide Seripa, Daniela Galimberti, Federico Licastro, Mark Lathrop, Hilkka Soininen, Philippe Amouyel

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Neurobiology of Aging
Volume	32
Issue number	4
DOIs	https://doi.org/10.1016/j.neurobiolaging.2010.11.022
Publication status	Published - Apr 2011

Keywords

Alzheimer
APOE
Association
BIN1
EXOC3L2
GWA
PICALM
Polymorphism
Risk

ASJC Scopus subject areas

Clinical Neurology
Neuroscience(all)
Ageing
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2010.11.022

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Lambert, J. C., Zelenika, D., Hiltunen, M., Chouraki, V., Combarros, O., Bullido, M. J., Tognoni, G., Fiévet, N., Boland, A., Arosio, B., Coto, E., Zompo, M. D., Mateo, I., Frank-Garcia, A., Helisalmi, S., Porcellini, E., Pilotto, A., Forti, P., Ferri, R., ... Amouyel, P. (2011). Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations. Neurobiology of Aging, 32(4). https://doi.org/10.1016/j.neurobiolaging.2010.11.022

Lambert, JC, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, MJ, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, MD, Mateo, I, Frank-Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossu, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H & Amouyel, P 2011, 'Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations', Neurobiology of Aging, vol. 32, no. 4. https://doi.org/10.1016/j.neurobiolaging.2010.11.022

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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.",

keywords = "Alzheimer, APOE, Association, BIN1, EXOC3L2, GWA, PICALM, Polymorphism, Risk",

author = "Lambert, {Jean Charles} and Diana Zelenika and Mikko Hiltunen and Vincent Chouraki and Onofre Combarros and Bullido, {Maria J.} and Gloria Tognoni and Nathalie Fi{\'e}vet and Anne Boland and Beatrice Arosio and Eliecer Coto and Zompo, {Maria Del} and Ignacio Mateo and Ana Frank-Garcia and Seppo Helisalmi and Elisa Porcellini and Alberto Pilotto and Paola Forti and Raffaele Ferri and Marc Delepine and Elio Scarpini and Gabriele Siciliano and Vincenzo Solfrizzi and Sandro Sorbi and Gianfranco Spalletta and Giovanni Ravaglia and Fernando Valdivieso and Victoria Alvarez and Paolo Bosco and Michelangelo Mancuso and Francesco Panza and Benedetta Nacmias and Paola Bossu and Paola Piccardi and Giorgio Annoni and Davide Seripa and Daniela Galimberti and Federico Licastro and Mark Lathrop and Hilkka Soininen and Philippe Amouyel",

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doi = "10.1016/j.neurobiolaging.2010.11.022",

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T1 - Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

AU - Lambert, Jean Charles

AU - Zelenika, Diana

AU - Hiltunen, Mikko

AU - Chouraki, Vincent

AU - Combarros, Onofre

AU - Bullido, Maria J.

AU - Tognoni, Gloria

AU - Fiévet, Nathalie

AU - Boland, Anne

AU - Arosio, Beatrice

AU - Coto, Eliecer

AU - Zompo, Maria Del

AU - Mateo, Ignacio

AU - Frank-Garcia, Ana

AU - Helisalmi, Seppo

AU - Porcellini, Elisa

AU - Pilotto, Alberto

AU - Forti, Paola

AU - Ferri, Raffaele

AU - Delepine, Marc

AU - Scarpini, Elio

AU - Siciliano, Gabriele

AU - Solfrizzi, Vincenzo

AU - Sorbi, Sandro

AU - Spalletta, Gianfranco

AU - Ravaglia, Giovanni

AU - Valdivieso, Fernando

AU - Alvarez, Victoria

AU - Bosco, Paolo

AU - Mancuso, Michelangelo

AU - Panza, Francesco

AU - Nacmias, Benedetta

AU - Bossu, Paola

AU - Piccardi, Paola

AU - Annoni, Giorgio

AU - Seripa, Davide

AU - Galimberti, Daniela

AU - Licastro, Federico

AU - Lathrop, Mark

AU - Soininen, Hilkka

AU - Amouyel, Philippe

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

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KW - APOE

KW - Association

KW - BIN1

KW - EXOC3L2

KW - GWA

KW - PICALM

KW - Polymorphism

KW - Risk

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JO - Neurobiology of Aging

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Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Abstract

Keywords

ASJC Scopus subject areas

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