Topic: Genetics and APOE
We identified four plasma protein level PGSs that were significantly associated (FDR-adjusted p < 0.05) with LOAD in a meta-analysis of the discovery and replication cohorts: CX3CL1, hepatocyte growth factor (HGF), TIE2, and matrix metalloproteinase-3 (MMP-3). When these four plasma proteins were used as exposures in MR with LOAD liability as the outcome, plasma levels of HGF were inferred to have a negative causal relationship with the disease when single-nucleotide polymorphisms (SNPs) used as instrumental variables were not restricted to cis-variants (OR/95%CI = 0.945/0.906-0.984, p = 0.005). Our results show that plasma HGF has a negative causal relationship with LOAD liability that is driven by pleiotropic SNPs possibly involved in other pathways. These findings suggest a low transferability between PGS and MR approaches, and future research should explore ways in which LOAD and the plasma proteome may interact.
Key findings
- We identified four plasma protein level PGSs that were significantly associated (FDR-adjusted p < 0.05) with LOAD in a meta-analysis of the discovery and replication cohorts: CX3CL1, hepatocyte growth factor (HGF), TIE2, and matrix metalloproteinase-3 (MMP-3).
- When these four plasma proteins were used as exposures in MR with LOAD liability as the outcome, plasma levels of HGF were inferred to have a negative causal relationship with the disease when single-nucleotide polymorphisms (SNPs) used as instrumental variables were not restricted to cis-variants (OR/95%CI = 0.945/0.906-0.984, p = 0.005).
- Our results show that plasma HGF has a negative causal relationship with LOAD liability that is driven by pleiotropic SNPs possibly involved in other pathways.
- These findings suggest a low transferability between PGS and MR approaches, and future research should explore ways in which LOAD and the plasma proteome may interact.
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Study details
- Study designmeta-analysis
- Participants17,747
- Evidence strengthHigh
How this study scored 84/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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, multi-centre collaboration and free to read, so those were left out: it earned 47 of the 56 points we could judge it on, which is 84 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in neuroscience) |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 17,747 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 39108314) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 47 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 47 of the 56 points we could judge it on is 84 out of 100. |
| Total | 84 / 100 | — |
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APA 7th
Cammann, D. B., Lu, Y., Rotter, J. I., Wood, A. C., & Chen, J. (2024). Polygenic scores and Mendelian randomization identify plasma proteins causally implicated in Alzheimer's disease. Frontiers in neuroscience. https://doi.org/10.3389/fnins.2024.1404377
Vancouver
Cammann DB, Lu Y, Rotter JI, Wood AC, Chen J. Polygenic scores and Mendelian randomization identify plasma proteins causally implicated in Alzheimer's disease. Frontiers in neuroscience. 2024. doi:10.3389/fnins.2024.1404377. PMID: 39108314.
BibTeX
@article{cammann2024-39108314,
author = {Cammann, Davis B and Lu, Yimei and Rotter, Jerome I and Wood, Alexis C and Chen, Jingchun},
title = {{Polygenic scores and Mendelian randomization identify plasma proteins causally implicated in Alzheimer's disease}},
journal = {Frontiers in neuroscience},
year = {2024},
doi = {10.3389/fnins.2024.1404377},
pmid = {39108314},
url = {https://doi.org/10.3389/fnins.2024.1404377}
}