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65/100

✓ Peer-reviewed alzhub usefulness score 65 out of 100. TREM2 and immune genetics

Topic: Brain proteins, microglia and lab models

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 ε4 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.

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APA 7th

Hooli, B. V., Parrado, A. R., Mullin, K., Yip, W. K., Liu, T., Roehr, J. T., et al. (2014). The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk. Neurology. https://doi.org/10.1212/wnl.0000000000000855

Vancouver

Hooli BV, Parrado AR, Mullin K, Yip WK, Liu T, Roehr JT, et al. The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk. Neurology. 2014. doi:10.1212/wnl.0000000000000855. PMID: 25186855.

BibTeX

@article{hooli2014-25186855,
  author  = {Hooli, B. V. and Parrado, A. R. and Mullin, K. and Yip, W. K. and Liu, T. and Roehr, J. T. and Qiao, D. and Jessen, F. and others},
  title   = {{The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk}},
  journal = {Neurology},
  year    = {2014},
  doi     = {10.1212/wnl.0000000000000855},
  pmid    = {25186855},
  url     = {https://doi.org/10.1212/wnl.0000000000000855}
}

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Key findings

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 ε4 allele.
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.

Why it matters

Testing family and case-control cohorts of Caucasian people, this study confirmed that the rare TREM2 R47H variant is associated with Alzheimer's risk (p value of 0.0029). However, the estimated effect (odds ratio of 1.67) was substantially smaller than first reported. This tempers earlier claims that R47H raises risk about as much as the APOE ε4 gene variant.

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Study details

Study designmeta-analysis
Evidence strengthHigh

How this study scored 65/100

Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Neurology)
Journal's citation record	4 / 4	Neurology: journal h-index 525 (OpenAlex, 2026-10-29)
Study design	12 / 12	A meta-analysis pooling many studies
Strength of evidence	5 / 5	Rated “high” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2014 — within 20 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	A review of other studies — randomization is not credited here
Times cited	4 / 7	Cited 44 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	3.1 citations a year over 14 year(s) since 2014
Impact for its field and year	3 / 6	Cited 4.1× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 17 other studies in this library
Still being cited	1 / 4	Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Rudolph E. Tanzi: h-index 145 (OpenAlex, whole career)
Institution's track record	3 / 3	Harvard University: institution h-index 3,235 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 6 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 25186855)
Free to read	0 / 2	Behind a paywall — scores zero
Total	65 / 100	—

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