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 journalArticlepeer-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 languageEnglish
JournalNeurobiology of Aging
Volume32
Issue number4
DOIs
Publication statusPublished - 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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