Topic: Genetics and APOE
Sequence models predict the molecular effects of genetic variation, yet their contribution to interpreting Alzheimer’s disease (AD) association signals remains uncertain. Here we analysed AlphaGenome Atlas predictions for 111,446 common variants across 75 regions from a European-ancestry genome-wide association study (GWAS) of AD and related dementias. Predicted expression effects modestly tracked association within loci (mean partial Spearman ρ = 0.018, P = 0.003) and were higher in variants with the highest posterior inclusion probability than in correlated variants outside credible sets (mean difference, 0.044 percentile units; P = 0.005). This relationship remained after adjustment for genic position (ρ = 0.011, P = 0.026). Predicted splicing effects also tracked association, but this relationship was attenuated after the adjustment. Expression and splicing scores were associated with the corresponding Genotype-Tissue Expression (GTEx) quantitative trait locus (QTL) status, although these analyses did not establish colocalization or agreement in allelic direction. Across 50 loci with multiple fine-mapping candidates, predicted cellular labels were no more concentrated than in position-matched comparisons, and expression direction profiles showed no detectable excess concordance with lead variants. These findings support expression predictions as complementary evidence for interpreting AD risk variants, while showing that the assignment of cellular context must account for fine-mapping uncertainty.
Key findings
- Expression and splicing scores were associated with the corresponding Genotype-Tissue Expression (GTEx) quantitative trait locus (QTL) status, although these analyses did not establish colocalization or agreement in allelic direction.
- These findings support expression predictions as complementary evidence for interpreting AD risk variants, while showing that the assignment of cellular context must account for fine-mapping uncertainty.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 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 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| 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 | 1 / 5 | Rated “low” 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 | — / 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 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 →
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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
Choi, B., & Jeong, J. (2026). Expression predictions inform molecular interpretation of Alzheimer’s disease risk loci. medRxiv. https://doi.org/10.64898/2026.10.07.26364928
Vancouver
Choi B, Jeong J. Expression predictions inform molecular interpretation of Alzheimer’s disease risk loci. medRxiv. 2026. doi:10.64898/2026.10.07.26364928.
BibTeX
@article{choi2026-49ca7993,
author = {Choi, B. and Jeong, J.},
title = {{Expression predictions inform molecular interpretation of Alzheimer’s disease risk loci}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.07.26364928},
url = {https://doi.org/10.64898/2026.10.07.26364928}
}
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