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The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis
Li R, Wang X, He P.. Experimental and therapeutic medicine, 2021-02-11
Topic: Brain proteins, microglia and lab models
Rare variants in the coding sequence of triggering receptor expressed on myeloid cells 2 (TREM2) have been identified in Alzheimer's disease (AD). They have been reported to be causative or confer risk of AD in several populations. However, the results are not conclusive. Therefore, a meta-analysis was performed to investigate the association between rare variants of TREM2 and the susceptibility to AD. Case-control studies meeting the inclusion criteria were identified by searching the PubMed, Embase and Web of Science databases. The association between four commonly analyzed variants of TREM2, p.Arg47His (R47H), p.Arg62His (R62H), p.Asp87Asn (D87N) and p.His157Tyr (H157Y), and the risk of AD were evaluated by meta-analyses with the fixed-effects model. Finally, a total of 26 datasets comprising 28,007 cases and 45,121 controls were included. There was no or low between-study heterogeneity in all comparisons. A significantly increased risk of AD was observed in carriers of R47H compared with non-carriers [odds ratio (OR)=3.88, 95% CI: 3.17-4.76, P<0.001], R62H (OR=1.37, 95% CI: 1.11-1.70, P=0.004) and H157Y (OR=4.22, 95% CI: 1.93-9.21, P<0.001). However, R62H only conferred a mild risk compared to R47H and H157Y (OR=1.37 vs. 3.88 and 4.22, respectively). D87N was not associated with AD susceptibility. Sensitivity analysis indicated that the association identified for R62H was not significant (P=0.192) when excluding a large-sample study. Subgroup analysis according to ethnicity revealed significant associations (R47H and H157Y) in Caucasians but not in Asians. In conclusion, rare coding variants of TREM2 were associated with an elevated risk of AD, particularly in Caucasians.
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APA 7th
Li, R., Wang, X., & He, P. (2021). The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis. Experimental and therapeutic medicine. https://doi.org/10.3892/etm.2021.9778
Vancouver
Li R, Wang X, He P. The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis. Experimental and therapeutic medicine. 2021. doi:10.3892/etm.2021.9778. PMID: 33732320.
BibTeX
@article{li2021-33732320,
author = {Li, R. and Wang, X. and He, P.},
title = {{The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis}},
journal = {Experimental and therapeutic medicine},
year = {2021},
doi = {10.3892/etm.2021.9778},
pmid = {33732320},
url = {https://doi.org/10.3892/etm.2021.9778}
}
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Key findings
- A significantly increased risk of AD was observed in carriers of R47H compared with non-carriers [odds ratio (OR)=3.88, 95% CI: 3.17-4.76, P<0.001], R62H (OR=1.37, 95% CI: 1.11-1.70, P=0.004) and H157Y (OR=4.22, 95% CI: 1.93-9.21, P<0.001).
- However, R62H only conferred a mild risk compared to R47H and H157Y (OR=1.37 vs. 3.88 and 4.22, respectively).
- D87N was not associated with AD susceptibility.
- Sensitivity analysis indicated that the association identified for R62H was not significant (P=0.192) when excluding a large-sample study.
- Subgroup analysis according to ethnicity revealed significant associations (R47H and H157Y) in Caucasians but not in Asians.
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Study details
- Study designmeta-analysis
- Participants26
- Effect sizeOR=1.37; OR=4.22
- Evidence strengthHigh
How this study scored 83/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 48 of the 58 points we could judge it on, which is 83 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental and therapeutic medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 26 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33732320) |
| Free to read | 2 / 2 | Free to read |
| Points | 48 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 48 of the 58 points we could judge it on is 83 out of 100. |
| Total | 83 / 100 | — |
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