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

Hussman Institute for Human Genomics

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

44 Scopus citations

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 (US)
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
State	Published - 2010

Keywords

Age at onset
Alzheimer's disease
apolipoprotein E
CALHM1
polymorphism

ASJC Scopus subject areas

Psychiatry and Mental health
Geriatrics and Gerontology
Clinical Psychology

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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

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease : A meta-analysis study. / Lambert, Jean Charles; Sleegers, Kristel; González-Pérez, Antonio; Ingelsson, Martin; Beecham, Gary W.; Hiltunen, Mikko; Combarros, Onofre; Bullido, Maria J.; Brouwers, Nathalie; Bettens, Karolien; Berr, Claudine; Pasquier, Florence; Richard, Florence; Dekosky, Steven T.; Hannequin, Didier; Haines, Jonathan L.; Tognoni, Gloria; Fiévet, Nathalie; Dartigues, Jean François; Tzourio, Christophe; Engelborghs, Sebastiaan; Arosio, Beatrice; Coto, Elicer; De Deyn, Peter; Del Zompo, Maria; Mateo, Ignacio; Boada, Merce; Antunez, Carmen; Lopez-Arrieta, Jesus; Epelbaum, Jacques; Schjeide, Brit Maren Michaud; Frank-Garcia, Ana; Giedraitis, Vilmentas; Helisalmi, Seppo; Porcellini, Elisa; Pilotto, Alberto; Forti, Paola; Ferri, Raffaele; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Scarpini, Elio; Siciliano, Gabriele; Solfrizzi, Vincenzo; Sorbi, Sandro; Spalletta, Gianfranco; Ravaglia, Giovanni; Valdivieso, Fernando; Vepsäläinen, Saila; Alvarez, Victoria; Bosco, Paolo; Mancuso, Michelangelo; Panza, Francesco; Nacmias, Benedetta; Bossù, Paola; Hanon, Olivier; Piccardi, Paola; Annoni, Giorgio; Mann, David; Marambaud, Philippe; Seripa, Davide; Galimberti, Daniela; Tanzi, Rudolph E.; Bertram, Lars; Lendon, Corinne; Lannfelt, Lars; Licastro, Federico; Campion, Dominique; Pericak-Vance, Margaret A.; Soininen, Hilkka; Van Broeckhoven, Christine; Alpérovitch, Annick; Ruiz, Agustin; Kamboh, M. Ilyas; Amouyel, Philippe.

In: Journal of Alzheimer's Disease, Vol. 22, No. 1, 2010, p. 247-255.

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

Lambert, JC, 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, JF, 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, BMM, 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

Lambert, Jean Charles ; Sleegers, Kristel ; González-Pérez, Antonio ; Ingelsson, Martin ; Beecham, Gary W. ; Hiltunen, Mikko ; Combarros, Onofre ; Bullido, Maria J. ; Brouwers, Nathalie ; Bettens, Karolien ; Berr, Claudine ; Pasquier, Florence ; Richard, Florence ; Dekosky, Steven T. ; Hannequin, Didier ; Haines, Jonathan L. ; Tognoni, Gloria ; Fiévet, Nathalie ; Dartigues, Jean François ; Tzourio, Christophe ; Engelborghs, Sebastiaan ; Arosio, Beatrice ; Coto, Elicer ; De Deyn, Peter ; Del Zompo, Maria ; Mateo, Ignacio ; Boada, Merce ; Antunez, Carmen ; Lopez-Arrieta, Jesus ; Epelbaum, Jacques ; Schjeide, Brit Maren Michaud ; Frank-Garcia, Ana ; Giedraitis, Vilmentas ; Helisalmi, Seppo ; Porcellini, Elisa ; Pilotto, Alberto ; Forti, Paola ; Ferri, Raffaele ; Delepine, Marc ; Zelenika, Diana ; Lathrop, Mark ; Scarpini, Elio ; Siciliano, Gabriele ; Solfrizzi, Vincenzo ; Sorbi, Sandro ; Spalletta, Gianfranco ; Ravaglia, Giovanni ; Valdivieso, Fernando ; Vepsäläinen, Saila ; Alvarez, Victoria ; Bosco, Paolo ; Mancuso, Michelangelo ; Panza, Francesco ; Nacmias, Benedetta ; Bossù, Paola ; Hanon, Olivier ; Piccardi, Paola ; Annoni, Giorgio ; Mann, David ; Marambaud, Philippe ; Seripa, Davide ; Galimberti, Daniela ; Tanzi, Rudolph E. ; Bertram, Lars ; Lendon, Corinne ; Lannfelt, Lars ; Licastro, Federico ; Campion, Dominique ; Pericak-Vance, Margaret A. ; Soininen, Hilkka ; Van Broeckhoven, Christine ; Alpérovitch, Annick ; Ruiz, Agustin ; Kamboh, M. Ilyas ; Amouyel, Philippe. / The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease : A meta-analysis study. In: Journal of Alzheimer's Disease. 2010 ; Vol. 22, No. 1. pp. 247-255.

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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.",

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AU - Licastro, Federico

AU - Campion, Dominique

AU - Pericak-Vance, Margaret A.

AU - Soininen, Hilkka

AU - Van Broeckhoven, Christine

AU - Alpérovitch, Annick

AU - Ruiz, Agustin

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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.

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