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 journalArticlepeer-review

45 Scopus citations


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 languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number1
StatePublished - 2010


  • 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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