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Shared genes between Alzheimer's disease and ischemic stroke
Wei CJ, Cui P, Li H, Lang WJ, Liu GY, Ma XF.. CNS neuroscience & therapeutics, 2019-03-11
Topic: Amyloid, tau and blood-test diagnosis
Aims Although converging evidence from experimental and epidemiological studies indicates Alzheimer's disease (AD) and ischemic stroke (IS) are related, the genetic basis underlying their links is less well characterized. Traditional SNP-based genome-wide association studies (GWAS) have failed to uncover shared susceptibility variants of AD and IS. Therefore, this study was designed to investigate whether pleiotropic genes existed between AD and IS to account for their phenotypic association, although this was not reported in previous studies. Methods Taking advantage of large-scale GWAS summary statistics of AD (17,008 AD cases and 37,154 controls) and IS (10,307 IS cases and 19,326 controls), we performed gene-based analysis implemented in VEGAS2 and Fisher's meta-analysis of the set of overlapped genes of nominal significance in both diseases. Subsequently, gene expression analysis in AD- or IS-associated expression datasets was conducted to explore the transcriptional alterations of pleiotropic genes identified. Results 16 AD-IS pleiotropic genes surpassed the cutoff for Bonferroni-corrected significance. Notably, MS4A4A and TREM2, two established AD-susceptibility genes showed remarkable alterations in the spleens and brains afflicted by IS, respectively. Among the prioritized genes identified by virtue of literature-based knowledge, most are immune-relevant genes (EPHA1, MS4A4A, UBE2L3 and TREM2), implicating crucial roles of the immune system in the pathogenesis of AD and IS. Conclusions The observation that AD and IS had shared disease-associated genes offered mechanistic insights into their common pathogenesis, predominantly involving the immune system. More importantly, our findings have important implications for future research directions, which are encouraged to verify the involvement of these candidates in AD and IS and interpret the exact molecular mechanisms of action.
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APA 7th
Wei, C. J., Cui, P., Li, H., Lang, W. J., Liu, G. Y., & Ma, X. F. (2019). Shared genes between Alzheimer's disease and ischemic stroke. CNS neuroscience & therapeutics. https://doi.org/10.1111/cns.13117
Vancouver
Wei CJ, Cui P, Li H, Lang WJ, Liu GY, Ma XF. Shared genes between Alzheimer's disease and ischemic stroke. CNS neuroscience & therapeutics. 2019. doi:10.1111/cns.13117. PMID: 30859738.
BibTeX
@article{wei2019-30859738,
author = {Wei, C. J. and Cui, P. and Li, H. and Lang, W. J. and Liu, G. Y. and Ma, X. F.},
title = {{Shared genes between Alzheimer's disease and ischemic stroke}},
journal = {CNS neuroscience \& therapeutics},
year = {2019},
doi = {10.1111/cns.13117},
pmid = {30859738},
url = {https://doi.org/10.1111/cns.13117}
}
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Key findings
- Results 16 AD-IS pleiotropic genes surpassed the cutoff for Bonferroni-corrected significance.
- More importantly, our findings have important implications for future research directions, which are encouraged to verify the involvement of these candidates in AD and IS and interpret the exact molecular mechanisms of action.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 69/100
Published in a peer-reviewed 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. 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 (CNS neuroscience & therapeutics) |
| 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 | 2 / 5 | 2019 — within 10 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) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30859738) |
| 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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