F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease
Tosto G, Fu H, Vardarajan BN, Lee JH, Cheng R, Reyes-Dumeyer D, Lantigua R, Medrano M et al.. Annals of clinical and translational neurology, 2015-06-18
Topic: Brain proteins, microglia and lab models
Objective In the context of late-onset Alzheimer's disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD. Methods About 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis. Significant loci were further tested in the expanded cohort that also included related family members (n = 5300). Two AD-like transgenic mice models (J20 and rTg4510) were used to study gene expression. Independent data sets of non-Hispanic Whites and African Americans were used to further validate findings, along with publicly available brain expression data sets. Results A novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case-control cohort (odd ratio [OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts (OR = 0.63, P = 4.7E-08). Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates. Publicly available microarray studies also showed significant overexpression of Fbxl7 in LOAD brains compared to nondemented controls. single-nucleotide polymorphism (SNP) rs75002042 was in complete linkage disequilibrium with other variants in two independent non-Hispanic White and African American data sets (0.0005 < P < 0.02) used for replication. Interpretation FBXL7, encodes a subcellular protein involved in phosphorylation-dependent ubiquitination processes and displays proapoptotic activity. F-box proteins also modulate inflammation and innate immunity, which may be important in LOAD pathogenesis. Further investigations are needed to validate and understand its role in this and other populations.
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APA 7th
Tosto, G., Fu, H., Vardarajan, B. N., Lee, J. H., Cheng, R., Reyes-Dumeyer, D., et al. (2015). F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease. Annals of clinical and translational neurology. https://doi.org/10.1002/acn3.223
Vancouver
Tosto G, Fu H, Vardarajan BN, Lee JH, Cheng R, Reyes-Dumeyer D, et al. F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease. Annals of clinical and translational neurology. 2015. doi:10.1002/acn3.223. PMID: 26339675.
BibTeX
@article{tosto2015-26339675,
author = {Tosto, G. and Fu, H. and Vardarajan, B. N. and Lee, J. H. and Cheng, R. and Reyes-Dumeyer, D. and Lantigua, R. and Medrano, M. and others},
title = {{F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease}},
journal = {Annals of clinical and translational neurology},
year = {2015},
doi = {10.1002/acn3.223},
pmid = {26339675},
url = {https://doi.org/10.1002/acn3.223}
}
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Key findings
- We aimed to identify novel loci associated with LOAD.
- Significant loci were further tested in the expanded cohort that also included related family members (n = 5300).
- Results A novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case-control cohort (odd ratio [OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts (OR = 0.63, P = 4.7E-08).
- Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates.
- Publicly available microarray studies also showed significant overexpression of Fbxl7 in LOAD brains compared to nondemented controls. single-nucleotide polymorphism (SNP) rs75002042 was in complete linkage disequilibrium with other variants in two independent non-Hispanic White and African American data sets (0.0005 < P < 0.02) used for replication.
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Study details
- Study designcase-control study
- Participants5,300
- Effect sizeOR = 0.63
- Evidence strengthModerate
How this study scored 69/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for 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 40 of the 58 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Annals of clinical and translational neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 5,300 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) |
| 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 26339675) |
| Free to read | 2 / 2 | Free to read |
| Points | 40 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 40 of the 58 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
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