TREM2 R47H variant and risk of essential tremor: A cross-sectional international multicenter study

Sara Ortega-Cubero, Oswaldo Lorenzo-Betancor, Elena Lorenzo, José A.G. Agúndez, Félix J. Jiménez-Jiménez, Owen A. Ross, Isabel Wurster, Carina Mielke, Juei Jueng Lin, Francisco Coria, Jordi Clarimon, Mario Ezquerra, Laura Brighina, Grazia Annesi, Hortensia Alonso-Navarro, Elena García-Martin, Alex Gironell, Maria J. Marti, Kuo Chu Yueh, Zbigniew K. WszolekManu Sharma, Daniela Berg, Rejko Krüger, Maria A. Pastor, Pau Pastor

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Introduction: Essential tremor (ET) is the most frequent movement disorder in adults. Its pathophysiology is not clearly understood, however there is growing evidence showing common etiologic factors with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (AD, PD). Recently, a rare p.R47H substitution (rs75932628) in the TREM2 protein (triggering receptor expressed on myeloid cells 2; OMIM: *605086) has been proposed as a risk factor for AD, PD and amyotrophic lateral sclerosis (ALS). The objective of the study was to determine whether TREM2 p.R47H allele is also a risk factor for developing ET. Methods: This was a cross-sectional multicenter international study. An initial case-control cohort from Spain (n=456 ET, n=2715 controls) was genotyped. In a replication phase, a case-control series (n=897 ET, n=1449 controls) from different populations (Italy, Germany, North-America and Taiwan) was studied. Owed to the rarity of the variant, published results on p.R47H allele frequency from 14777 healthy controls from European, North American or Chinese descent were additionally considered. The main outcome measure was p.R47H (rs75932628) allelic frequency. Results: There was a significant association between TREM2 p.R47H variant and ET in the Spanish cohort (odds ratio [OR], 5.97; 95% CI, 1.203-29.626; p=0.042), but it was not replicated in other populations. Conclusions: These results argue in favor of population-specific differences in the allelic distribution and suggest that p.R47H (rs75932628) variant may contribute to the susceptibility of ET in Spanish population. However, taking into account the very low frequency of p.R47H, further confirmatory analyses of larger ET series are needed.

Original languageEnglish (US)
Pages (from-to)306-309
Number of pages4
JournalParkinsonism and Related Disorders
Issue number3
StatePublished - Mar 1 2015


  • Essential tremor
  • Genetics
  • P.R47H
  • Risk
  • TREM2

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology


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