The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Jean-Charles Lambert; Kristel Sleegers; Antonio González-Pérez; Martin Ingelsson; Gary W Beecham; Mikko Hiltunen; Onofre Combarros; Maria J Bullido; Nathalie Brouwers; Karolien Bettens; Claudine Berr; Florence Pasquier; Florence Richard; Steven T Dekosky; Didier Hannequin; Jonathan L Haines; Gloria Tognoni; Nathalie Fiévet; Jean-François Dartigues; Christophe Tzourio; Sebastiaan Engelborghs; Beatrice Arosio; Elicer Coto; Peter De Deyn; Maria Del Zompo; Ignacio Mateo; Merce Boada; Carmen Antunez; Jesus Lopez-Arrieta; Jacques Epelbaum; Brit-Maren Michaud Schjeide; Ana Frank-Garcia; Vilmentas Giedraitis; Seppo Helisalmi; Elisa Porcellini; Alberto Pilotto; Paola Forti; Raffaele Ferri; Marc Delepine; Diana Zelenika; Mark Lathrop; Elio Scarpini; Gabriele Siciliano; Vincenzo Solfrizzi; Sandro Sorbi; Gianfranco Spalletta; Giovanni Ravaglia; Fernando Valdivieso; Saila Vepsäläinen; Victoria Alvarez; Paolo Bosco; Michelangelo Mancuso; Francesco Panza; Benedetta Nacmias; Paola Bossù; Olivier Hanon; Paola Piccardi; Giorgio Annoni; David Mann; Philippe Marambaud; Davide Seripa; Daniela Galimberti; Rudolph E Tanzi; Lars Bertram; Corinne Lendon; Lars Lannfelt; Federico Licastro; Dominique Campion; Margaret A Pericak-Vance; Hilkka Soininen; Christine Van Broeckhoven; Annick Alpérovitch; Agustin Ruiz; M Ilyas Kamboh; Philippe Amouyel

doi:10.3233/JAD-2010-100933

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Jean-Charles Lambert, Kristel Sleegers, Antonio González-Pérez, Martin Ingelsson, Gary W Beecham, Mikko Hiltunen, Onofre Combarros, Maria J Bullido, Nathalie Brouwers, Karolien Bettens, Claudine Berr, Florence Pasquier, Florence Richard, Steven T Dekosky, Didier Hannequin, Jonathan L Haines, Gloria Tognoni, Nathalie Fiévet, Jean-François Dartigues, Christophe TzourioSebastiaan Engelborghs, Beatrice Arosio, Elicer Coto, Peter De Deyn, Maria Del Zompo, Ignacio Mateo, Merce Boada, Carmen Antunez, Jesus Lopez-Arrieta, Jacques Epelbaum, Brit-Maren Michaud Schjeide, Ana Frank-Garcia, Vilmentas Giedraitis, Seppo Helisalmi, Elisa Porcellini, Alberto Pilotto, Paola Forti, Raffaele Ferri, Marc Delepine, Diana Zelenika, Mark Lathrop, Elio Scarpini, Gabriele Siciliano, Vincenzo Solfrizzi, Sandro Sorbi, Gianfranco Spalletta, Giovanni Ravaglia, Fernando Valdivieso, Saila Vepsäläinen, Victoria Alvarez, Paolo Bosco, Michelangelo Mancuso, Francesco Panza, Benedetta Nacmias, Paola Bossù, Olivier Hanon, Paola Piccardi, Giorgio Annoni, David Mann, Philippe Marambaud, Davide Seripa, Daniela Galimberti, Rudolph E Tanzi, Lars Bertram, Corinne Lendon, Lars Lannfelt, Federico Licastro, Dominique Campion, Margaret A Pericak-Vance, Hilkka Soininen, Christine Van Broeckhoven, Annick Alpérovitch, Agustin Ruiz, M Ilyas Kamboh, Philippe Amouyel

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

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Abstract

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.

Original language	English
Pages (from-to)	247-255
Number of pages	9
Journal	Journal of Alzheimer's Disease
Volume	22
Issue number	1
DOIs	https://doi.org/10.3233/JAD-2010-100933
Publication status	Published - 2010

Keywords

Age of Onset
Aged
Aged, 80 and over
Alleles
Alzheimer Disease/epidemiology
Apolipoprotein E4/genetics
Calcium Channels/genetics
Case-Control Studies
Female
Humans
Male
Membrane Glycoproteins/genetics
Middle Aged
Polymorphism, Genetic/genetics

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Lambert, J.-C., Sleegers, K., González-Pérez, A., Ingelsson, M., Beecham, G. W., Hiltunen, M., Combarros, O., Bullido, M. J., Brouwers, N., Bettens, K., Berr, C., Pasquier, F., Richard, F., Dekosky, S. T., Hannequin, D., Haines, J. L., Tognoni, G., Fiévet, N., Dartigues, J.-F., ... Amouyel, P. (2010). The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study. Journal of Alzheimer's Disease, 22(1), 247-255. https://doi.org/10.3233/JAD-2010-100933

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title = "The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study",

abstract = "The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.",

keywords = "Age of Onset, Aged, Aged, 80 and over, Alleles, Alzheimer Disease/epidemiology, Apolipoprotein E4/genetics, Calcium Channels/genetics, Case-Control Studies, Female, Humans, Male, Membrane Glycoproteins/genetics, Middle Aged, Polymorphism, Genetic/genetics",

author = "Jean-Charles Lambert and Kristel Sleegers and Antonio Gonz{\'a}lez-P{\'e}rez and Martin Ingelsson and Beecham, {Gary W} and Mikko Hiltunen and Onofre Combarros and Bullido, {Maria J} and Nathalie Brouwers and Karolien Bettens and Claudine Berr and Florence Pasquier and Florence Richard and Dekosky, {Steven T} and Didier Hannequin and Haines, {Jonathan L} and Gloria Tognoni and Nathalie Fi{\'e}vet and Jean-Fran{\c c}ois Dartigues and Christophe Tzourio and Sebastiaan Engelborghs and Beatrice Arosio and Elicer Coto and {De Deyn}, Peter and {Del Zompo}, Maria and Ignacio Mateo and Merce Boada and Carmen Antunez and Jesus Lopez-Arrieta and Jacques Epelbaum and Schjeide, {Brit-Maren Michaud} and Ana Frank-Garcia and Vilmentas Giedraitis and Seppo Helisalmi and Elisa Porcellini and Alberto Pilotto and Paola Forti and Raffaele Ferri and Marc Delepine and Diana Zelenika and Mark Lathrop and Elio Scarpini and Gabriele Siciliano and Vincenzo Solfrizzi and Sandro Sorbi and Gianfranco Spalletta and Giovanni Ravaglia and Fernando Valdivieso and Saila Veps{\"a}l{\"a}inen and Victoria Alvarez and Paolo Bosco and Michelangelo Mancuso and Francesco Panza and Benedetta Nacmias and Paola Boss{\`u} and Olivier Hanon and Paola Piccardi and Giorgio Annoni and David Mann and Philippe Marambaud and Davide Seripa and Daniela Galimberti and Tanzi, {Rudolph E} and Lars Bertram and Corinne Lendon and Lars Lannfelt and Federico Licastro and Dominique Campion and Pericak-Vance, {Margaret A} and Hilkka Soininen and {Van Broeckhoven}, Christine and Annick Alp{\'e}rovitch and Agustin Ruiz and Kamboh, {M Ilyas} and Philippe Amouyel",

year = "2010",

doi = "10.3233/JAD-2010-100933",

language = "English",

volume = "22",

pages = "247--255",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "IOS Press",

number = "1",

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Lambert, J-C, Sleegers, K, González-Pérez, A, Ingelsson, M, Beecham, GW, Hiltunen, M, Combarros, O, Bullido, MJ, Brouwers, N, Bettens, K, Berr, C, Pasquier, F, Richard, F, Dekosky, ST, Hannequin, D, Haines, JL, Tognoni, G, Fiévet, N, Dartigues, J-F, Tzourio, C, Engelborghs, S, Arosio, B, Coto, E, De Deyn, P, Del Zompo, M, Mateo, I, Boada, M, Antunez, C, Lopez-Arrieta, J, Epelbaum, J, Schjeide, B-MM, Frank-Garcia, A, Giedraitis, V, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Zelenika, D, Lathrop, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Vepsäläinen, S, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Hanon, O, Piccardi, P, Annoni, G, Mann, D, Marambaud, P, Seripa, D, Galimberti, D, Tanzi, RE, Bertram, L, Lendon, C, Lannfelt, L, Licastro, F, Campion, D, Pericak-Vance, MA, Soininen, H, Van Broeckhoven, C, Alpérovitch, A, Ruiz, A, Kamboh, MI & Amouyel, P 2010, 'The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study', Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 247-255. https://doi.org/10.3233/JAD-2010-100933

TY - JOUR

T1 - The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease

T2 - a meta-analysis study

AU - Lambert, Jean-Charles

AU - Sleegers, Kristel

AU - González-Pérez, Antonio

AU - Ingelsson, Martin

AU - Beecham, Gary W

AU - Hiltunen, Mikko

AU - Combarros, Onofre

AU - Bullido, Maria J

AU - Brouwers, Nathalie

AU - Bettens, Karolien

AU - Berr, Claudine

AU - Pasquier, Florence

AU - Richard, Florence

AU - Dekosky, Steven T

AU - Hannequin, Didier

AU - Haines, Jonathan L

AU - Tognoni, Gloria

AU - Fiévet, Nathalie

AU - Dartigues, Jean-François

AU - Tzourio, Christophe

AU - Engelborghs, Sebastiaan

AU - Arosio, Beatrice

AU - Coto, Elicer

AU - De Deyn, Peter

AU - Del Zompo, Maria

AU - Mateo, Ignacio

AU - Boada, Merce

AU - Antunez, Carmen

AU - Lopez-Arrieta, Jesus

AU - Epelbaum, Jacques

AU - Schjeide, Brit-Maren Michaud

AU - Frank-Garcia, Ana

AU - Giedraitis, Vilmentas

AU - Helisalmi, Seppo

AU - Porcellini, Elisa

AU - Pilotto, Alberto

AU - Forti, Paola

AU - Ferri, Raffaele

AU - Delepine, Marc

AU - Zelenika, Diana

AU - Lathrop, Mark

AU - Scarpini, Elio

AU - Siciliano, Gabriele

AU - Solfrizzi, Vincenzo

AU - Sorbi, Sandro

AU - Spalletta, Gianfranco

AU - Ravaglia, Giovanni

AU - Valdivieso, Fernando

AU - Vepsäläinen, Saila

AU - Alvarez, Victoria

AU - Bosco, Paolo

AU - Mancuso, Michelangelo

AU - Panza, Francesco

AU - Nacmias, Benedetta

AU - Bossù, Paola

AU - Hanon, Olivier

AU - Piccardi, Paola

AU - Annoni, Giorgio

AU - Mann, David

AU - Marambaud, Philippe

AU - Seripa, Davide

AU - Galimberti, Daniela

AU - Tanzi, Rudolph E

AU - Bertram, Lars

AU - Lendon, Corinne

AU - Lannfelt, Lars

AU - Licastro, Federico

AU - Campion, Dominique

AU - Pericak-Vance, Margaret A

AU - Soininen, Hilkka

AU - Van Broeckhoven, Christine

AU - Alpérovitch, Annick

AU - Ruiz, Agustin

AU - Kamboh, M Ilyas

AU - Amouyel, Philippe

PY - 2010

Y1 - 2010

N2 - The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.

AB - The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.

KW - Age of Onset

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Alzheimer Disease/epidemiology

KW - Apolipoprotein E4/genetics

KW - Calcium Channels/genetics

KW - Case-Control Studies

KW - Female

KW - Humans

KW - Male

KW - Membrane Glycoproteins/genetics

KW - Middle Aged

KW - Polymorphism, Genetic/genetics

U2 - 10.3233/JAD-2010-100933

DO - 10.3233/JAD-2010-100933

M3 - Article

C2 - 20847397

SN - 1387-2877

VL - 22

SP - 247

EP - 255

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 1

ER -

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Abstract

Keywords

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