Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

Agustín Ruiz, Oriol Dols-Icardo, María J. Bullido, Pau Pastor, Eloy Rodríguez-Rodríguez, Adolfo López de Munain, Marian M. de Pancorbo, Jordi Pérez-Tur, Victoria Álvarez, Anna Antonell, Jesús López-Arrieta, Isabel Hernández, Lluís Tárraga, Mercè Boada, Alberto Lleó, Rafael Blesa, Ana Frank-García, Isabel Sastre, Cristina Razquin, Sara Ortega-CuberoElena Lorenzo, Pascual Sánchez-Juan, Onofre Combarros, Fermín Moreno, Ana Gorostidi, Xabier Elcoroaristizabal, Miquel Baquero, Eliecer Coto, Raquel Sánchez-Valle, Jordi Clarimón

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84 Citations (Scopus)


A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR]= 4.12, 95% confidence interval [CI]= 1.21-14.00, p= 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR= 4.11, 95% CI= 2.99-5.68, p= 5.27×10-18). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD. © 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)444.e1-444.e4
JournalNeurobiology of Aging
Issue number2
Publication statusPublished - 1 Jan 2014


  • Alzheimer's disease
  • Frontotemporal dementia
  • Genetic association
  • P.R47H
  • Rare variant
  • TREM2


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