The rare TREM2 R47H variant exerts only a modest effect on alzheimer disease risk

Basavaraj V. Hooli, Antonio R. Parrado, Kristina Mullin, Wai Ki Yip, Tian Liu, Johannes T. Roehr, Dandi Qiao, Frank Jessen, Oliver Peters, Tim Becker, Alfredo Ramirez, Christoph Lange, Lars Bertram, Rudolph E. Tanzi*

*Corresponding author for this work
20 Citations (Scopus)


Objectives: Recently, 2 independent studies reported that a rare missense variant, rs75932628 (R47H), in exon 2 of the gene encoding the "triggering receptor expressed on myeloid cells 2" (TREM2) significantly increases the risk of Alzheimer disease (AD) with an effect size comparable to that of the APOE e4 allele. Methods: In this study, we attempted to replicate the association between rs75932628 and AD risk by directly genotyping rs75932628 in 2 independent Caucasian family cohorts consisting of 927 families (with 1,777 affected and 1,235 unaffected) and in 2 Caucasian case-control cohorts composed of 1,314 cases and 1,609 controls. In addition, we imputed genotypes in 3 independent Caucasian case-control cohorts containing 1,906 cases and 1,503 controls. Results: Meta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95-2.92) for the association between the TREM2 R47H and increased AD risk. Conclusions: While our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported.

Original languageEnglish
Issue number15
Pages (from-to)1353-1358
Number of pages6
Publication statusPublished - 01.01.2014

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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