Topic: Brain proteins, microglia and lab models
Polygenic and proteomic risk scores are both proposed for pre-symptomatic stratification, yet the extent to which they provide overlapping or complementary information has not been measured across neurodegenerative disease. To quantify this overlap, we define absorption as the fraction of a polygenic scores predictive contribution accounted for by an out-of-fold proteomic score and estimate it among 9,434 to 9,820 UK Biobank participants. Absorption did not track h2, as Alzheimers with APOE, Alzheimers without APOE and Parkinsons carried matched SNP h2 of 0.068, 0.061 and 0.069 yet absorbed 0.73, 0.39 and 0.19, with amyotrophic lateral sclerosis at 0.22. Residual genetic signal remained in all four, indicating that proteomic risk scores did not fully capture the predictive information contained in polygenic risk scores. The proteins associated with a polygenic score and the proteins a proteomic score selects overlap no more often than chance, converging only where APOE dominates. Across 33 plasma co-expression modules built in 41,358 disease-free participants, germline signal concentrates in modules rather than spreading, with the summary component of seven modules associated with the score for Alzheimers with APOE and none for Parkinsons, even though Parkinsons carries the lysosomal genetic architecture that the lysosomal module M32 encodes. This module has 89% of its members associated with AD germline risk yet none was used by the proteomic score. Rebuilding the co-expression modules in All of Us gave an adjusted Rand index of 0.582 against the 0.686 attainable within that cohort, and 29 of 33 modules stayed together above a permutation null. Cross-cohort transferability was predictable from module coherence in the discovery cohort, supporting the reuse of this module partition as a fixed reference dictionary.
Key findings
- The proteins associated with a polygenic score and the proteins a proteomic score selects overlap no more often than chance, converging only where APOE dominates.
- Across 33 plasma co-expression modules built in 41,358 disease-free participants, germline signal concentrates in modules rather than spreading, with the summary component of seven modules associated with the score for Alzheimers with APOE and none for Parkinsons, even though Parkinsons carries the
- This module has 89% of its members associated with AD germline risk yet none was used by the proteomic score.
Why it matters
This study found that polygenic and proteomic risk scores for neurodegenerative diseases overlap no more often than chance except where APOE dominates, and that genetic signal concentrates in specific plasma co-expression modules. It concerns risk score methodology, not treating, curing or preventing Alzheimer's disease.
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Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 22 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 impact for its field and year, so that was left out: it earned 21 of the 94 points we could judge it on, which is 22 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Dokyoon Kim: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 21 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 21 of the 94 points we could judge it on is 22 out of 100. |
| Total | 22 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Zheng, C., Shivakumar, M., Shen, L., & Kim, D. (2026). Absorption and Co-expression Modules Show Where Polygenic and Proteomic Risk Scores Diverge in Neurodegenerative Diseases. medRxiv (preprint). https://doi.org/10.64898/2026.08.24.26361271
Vancouver
Zheng C, Shivakumar M, Shen L, Kim D. Absorption and Co-expression Modules Show Where Polygenic and Proteomic Risk Scores Diverge in Neurodegenerative Diseases. medRxiv (preprint). 2026. doi:10.64898/2026.08.24.26361271.
BibTeX
@article{zheng2026-e4fc5f6b,
author = {Zheng, C. and Shivakumar, M. and Shen, L. and Kim, D.},
title = {{Absorption and Co-expression Modules Show Where Polygenic and Proteomic Risk Scores Diverge in Neurodegenerative Diseases}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.24.26361271},
url = {https://doi.org/10.64898/2026.08.24.26361271}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.