Topic: Genetics and APOE
Inverse-variance weighted MR indicated that genetically predicted focal epilepsy with hippocampal sclerosis was associated with increased odds of AD (OR=3.99, 95% CI 1.17–13.61; P=0.027). No heterogeneity was detected (Cochran’s Q=0.006, P=0.939; I²=0%). In the UK Biobank epilepsy GWAS, 95 variants reached the suggestive threshold (P<5×10⁻⁶). The strongest shared signal was rs429358 in APOE, which approached genome-wide significance in epilepsy (OR=1.12, 95% CI 1.07–1.16; P=5.48×10⁻⁸) and showed a substantially stronger association with AD (OR=1.67, 95% CI 1.65–1.70; P=2.23×10⁻³⁰⁷). At P < 5 × 10⁻⁶, rs429358 was the only overlapping variant between the two GWAS results. Colocalization of 1,113 harmonized variants at the chromosome 19 APOE locus strongly supported a shared association signal (PP.H4=0.99994), with rs429358 carrying virtually all variant-level posterior probability. MAGMA identified 32 Bonferroni-significant genes and 10 significant gene sets in AD, whereas none survived correction in epilepsy. Using large-scale datasets, including UK Biobank and IEU data, these findings provide preliminary evidence that epilepsy may increase AD susceptibility and identify rs429358 as a potential overlap SNP with shared potential biological signal pathways. Larger epilepsy datasets and independent replication are required.
Key findings
- Inverse-variance weighted MR indicated that genetically predicted focal epilepsy with hippocampal sclerosis was associated with increased odds of AD (OR=3.99, 95% CI 1.17–13.61; P=0.027).
- No heterogeneity was detected (Cochran’s Q=0.006, P=0.939; I²=0%).
- In the UK Biobank epilepsy GWAS, 95 variants reached the suggestive threshold (P<5×10⁻⁶).
- The strongest shared signal was rs429358 in APOE, which approached genome-wide significance in epilepsy (OR=1.12, 95% CI 1.07–1.16; P=5.48×10⁻⁸) and showed a substantially stronger association with AD (OR=1.67, 95% CI 1.65–1.70; P=2.23×10⁻³⁰⁷).
- At P < 5 × 10⁻⁶, rs429358 was the only overlapping variant between the two GWAS results.
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Study details
- Participants803
- Effect sizeOR=3.99; OR=1.12; OR=1.67
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 34 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design 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 21 of the 62 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 2 / 4 | 803 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 21 of the 62 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Ren, Y., He, Z., Feng, Y., Wang, R., Cai, H., Chen, Q., et al. (2026). Large-Scale Genome-wide association study identified Shared Genetic Risk SNPs Correlates in Epilepsy and Alzheimer's Disease. Research Square. https://doi.org/10.21203/rs.3.rs-10960127/v1
Vancouver
Ren Y, He Z, Feng Y, Wang R, Cai H, Chen Q, et al. Large-Scale Genome-wide association study identified Shared Genetic Risk SNPs Correlates in Epilepsy and Alzheimer's Disease. Research Square. 2026. doi:10.21203/rs.3.rs-10960127/v1.
BibTeX
@article{ren2026-b1e4c121,
author = {Ren, Y. and He, Z. and Feng, Y. and Wang, R. and Cai, H. and Chen, Q. and Wang, M.},
title = {{Large-Scale Genome-wide association study identified Shared Genetic Risk SNPs Correlates in Epilepsy and Alzheimer's Disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10960127/v1},
url = {https://doi.org/10.21203/rs.3.rs-10960127/v1}
}
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