Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases
Gagliano SA, Pouget JG, Hardy J, Knight J, Barnes MR, Ryten M, Weale ME.. Annals of clinical and translational neurology, 2016-11-04
Topic: Amyloid, tau and blood-test diagnosis
Objectives We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene-set lists were enriched for genetic heritability. We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr). Results There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g., T cells) for PD, and from both the adaptive (e.g., T cells) and innate (e.g., CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results. Interpretation For AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.
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APA 7th
Gagliano, S. A., Pouget, J. G., Hardy, J., Knight, J., Barnes, M. R., Ryten, M., et al. (2016). Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases. Annals of clinical and translational neurology. https://doi.org/10.1002/acn3.369
Vancouver
Gagliano SA, Pouget JG, Hardy J, Knight J, Barnes MR, Ryten M, et al. Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases. Annals of clinical and translational neurology. 2016. doi:10.1002/acn3.369. PMID: 28097204.
BibTeX
@article{gagliano2016-28097204,
author = {Gagliano, S. A. and Pouget, J. G. and Hardy, J. and Knight, J. and Barnes, M. R. and Ryten, M. and Weale, M. E.},
title = {{Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases}},
journal = {Annals of clinical and translational neurology},
year = {2016},
doi = {10.1002/acn3.369},
pmid = {28097204},
url = {https://doi.org/10.1002/acn3.369}
}
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Key findings
- We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr).
- Results There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems.
- We found this for MS (as expected) and also for AD and PD.
- Annotations from the liver were also significant for AD.
- Pathway analysis provided complementary results.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, 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 (Annals of clinical and translational neurology) |
| 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 | 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 | 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 28097204) |
| Free to read | 2 / 2 | Free to read |
| 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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