Pathway-Specific Polygenic Risk Scores Correlate with Clinical Status and Alzheimer's Disease-Related Biomarkers
Nicholas J Schork, Jeremy A Elman, Alzheimer’s Disease Neuroimaging Initiative. Journal of Alzheimer's disease : JAD, 2023
Topic: Genetics and APOE
Thirteen pathway clusters were identified, and eight pathway-specific PRSs were significantly associated with AD diagnosis. Amyloid-positivity was associated with endocytosis and fibril formation, response misfolded protein, and regulation protein tyrosine PRSs. Ptau positivity and hippocampal volume were both related to protein localization and mitophagy PRS, and ptau-positivity was also associated with an immune signaling PRS. A global AD PRS showed stronger associations with diagnosis and all biomarkers compared to pathway PRSs. Pathway PRS may contribute to understanding separable disease processes, but do not add significant power for predictive purposes. These findings demonstrate that AD-phenotypes may be preferentially associated with risk in specific pathways, and defining genetic risk along multiple dimensions may clarify etiological heterogeneity in AD. This approach to delineate pathway-specific PRS can be used to study other complex diseases.
Key findings
- Thirteen pathway clusters were identified, and eight pathway-specific PRSs were significantly associated with AD diagnosis.
- Amyloid-positivity was associated with endocytosis and fibril formation, response misfolded protein, and regulation protein tyrosine PRSs.
- Ptau positivity and hippocampal volume were both related to protein localization and mitophagy PRS, and ptau-positivity was also associated with an immune signaling PRS.
- A global AD PRS showed stronger associations with diagnosis and all biomarkers compared to pathway PRSs.
- Pathway PRS may contribute to understanding separable disease processes, but do not add significant power for predictive purposes.
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Study details
- Participants1,411
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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, multi-centre collaboration and free to read, so those were left out: it earned 29 of the 56 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,411 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 | 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 37661888) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 29 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 29 of the 56 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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APA 7th
Schork, N. J., Elman, J. A., & Alzheimer’s Disease Neuroimaging Initiative. (2023). Pathway-Specific Polygenic Risk Scores Correlate with Clinical Status and Alzheimer's Disease-Related Biomarkers. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-230548
Vancouver
Schork NJ, Elman JA, Alzheimer’s Disease Neuroimaging Initiative. Pathway-Specific Polygenic Risk Scores Correlate with Clinical Status and Alzheimer's Disease-Related Biomarkers. Journal of Alzheimer's disease : JAD. 2023. doi:10.3233/jad-230548. PMID: 37661888.
BibTeX
@article{schork2023-37661888,
author = {Schork, Nicholas J and Elman, Jeremy A and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Pathway-Specific Polygenic Risk Scores Correlate with Clinical Status and Alzheimer's Disease-Related Biomarkers}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2023},
doi = {10.3233/jad-230548},
pmid = {37661888},
url = {https://doi.org/10.3233/jad-230548}
}