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Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set
Ghani M, Sato C, Kakhki EG, Gibbs JR, Traynor B, St George-Hyslop P, Rogaeva E.. Neurobiology of aging, 2016-03-21
Topic: Amyloid, tau and blood-test diagnosis
Genome wide association studies have identified an association between Alzheimer's disease (AD) and common polymorphisms in the MS4A and TREM loci (each containing a cluster of homologous genes) and should be thoroughly investigated for the presence of potentially functional variations. We conducted a mutation analysis by next generation sequencing of 15 genes within the MS4A and TREM gene clusters; and catalogued rare coding variants detected in a North American data set of 210 cases and 233 controls. Investigation of the 5 homologues genes in the TREM locus revealed potentially damaging rare variants in TREM2, TREML1, TREML2, and TREML4. In agreement with a previous report, we observed a significant enrichment of TREM2-damaging missense substitutions in cases (N = 9; 4.2%) compared with controls (N=2; 0.9%; p = 0.010; after Yates' correction p = 0.022). Among known AD-associated TREM2 substitutions, we detected p.R47H, p.D87N, and p.H157Y affecting both TREM2 isoforms (NM_018965 and NM_001271821). In addition, we identified 2 cases with novel TREM2 variants (p.L205P and p.G219C), which mapped only to the isoform NM_001271821 at the C-terminus. Investigation of the MS4A gene cluster revealed that potentially damaging missense substitutions and loss-of-function variants were twice as frequent in controls (N = 19; 8.2%) than cases (N = 9; 4.3%), generating a nominally significant result (p = 0.047; after Yates' correction p = 0.07). Validation of our observation in large data sets might address the question whether such variants could contribute to the protective effect of the minor alleles of Genome wide association study-significant single nucleotide polymorphisms at the MS4A locus.
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APA 7th
Ghani, M., Sato, C., Kakhki, E. G., Gibbs, JR., Traynor, B., St George-Hyslop, P., et al. (2016). Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2016.03.009
Vancouver
Ghani M, Sato C, Kakhki EG, Gibbs JR, Traynor B, St George-Hyslop P, et al. Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set. Neurobiology of aging. 2016. doi:10.1016/j.neurobiolaging.2016.03.009. PMID: 27084067.
BibTeX
@article{ghani2016-27084067,
author = {Ghani, M. and Sato, C. and Kakhki, E. G. and Gibbs, JR. and Traynor, B. and St George-Hyslop, P. and Rogaeva, E.},
title = {{Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set}},
journal = {Neurobiology of aging},
year = {2016},
doi = {10.1016/j.neurobiolaging.2016.03.009},
pmid = {27084067},
url = {https://doi.org/10.1016/j.neurobiolaging.2016.03.009}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Investigation of the 5 homologues genes in the TREM locus revealed potentially damaging rare variants in TREM2, TREML1, TREML2, and TREML4.
- In agreement with a previous report, we observed a significant enrichment of TREM2-damaging missense substitutions in cases (N = 9; 4.2%) compared with controls (N=2; 0.9%; p = 0.010; after Yates' correction p = 0.022).
- Investigation of the MS4A gene cluster revealed that potentially damaging missense substitutions and loss-of-function variants were twice as frequent in controls (N = 19; 8.2%) than cases (N = 9; 4.3%), generating a nominally significant result (p = 0.047; after Yates' correction p = 0.07).
- Validation of our observation in large data sets might address the question whether such variants could contribute to the protective effect of the minor alleles of Genome wide association study-significant single nucleotide polymorphisms at the MS4A locus.
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Study details
- Effect size4.2%; 0.9%; 8.2%
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. 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 multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27084067) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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