Topic: Brain proteins, microglia and lab models
Structural variants (SVs) are a major source of genetic variation yet remain underexplored in healthy aging and neurodegenerative diseases. We performed nanopore long-read genome sequencing (lrGS) on 551 deeply-phenotyped individuals from Stanfords Aging and Memory Study and Alzheimers Disease Research Center, generating a comprehensive SV map integrated with matched methylation, transcriptomic, and proteomic data. Over 60% of SVs identified by lrGS were not detected with short-read WGS, including many poorly tagged by single-nucleotide variants (SNVs). We discovered >60,000 SV-QTLs across molecular traits and showed that SVs were more likely than SNVs to be fine-mapped as causal. Colocalization with Alzheimers and Parkinsons disease GWAS implicated SVs at multiple loci, including TMEM106B, BIN3, and NBEAL1. Multi-omic outlier enrichment and Bayesian modeling prioritized rare functional SVs near known risk genes. Combined, these data reveal widespread regulatory SVs in healthy aging and neurodegeneration, underscoring the importance of lrGS in deciphering complex genetic architecture.
Key findings
- We discovered >60,000 SV-QTLs across molecular traits and showed that SVs were more likely than SNVs to be fine-mapped as causal.
Why it matters
Long-read genome sequencing found many structural variants missed by short-read methods and implicated variants at loci including TMEM106B, BIN3 and NBEAL1 in Alzheimer's and Parkinson's disease. This is a genetic architecture study, not a treatment or prevention trial.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 28 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 26 of the 94 points we could judge it on, which is 28 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 | 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 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 | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michael D. Greicius: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 26 of the 94 points we could judge it on is 28 out of 100. |
| Total | 28 / 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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Jensen, T. D., Le Guen, Y., Talozzi, L., Yang, S., Gorzynski, J., Pena-Tauber, A., et al. (2026). Long-read genome sequencing and multi-omics in aging and neurodegeneration. medRxiv (preprint). https://doi.org/10.1101/2025.10.10.25337775
Vancouver
Jensen TD, Le Guen Y, Talozzi L, Yang S, Gorzynski J, Pena-Tauber A, et al. Long-read genome sequencing and multi-omics in aging and neurodegeneration. medRxiv (preprint). 2026. doi:10.1101/2025.10.10.25337775.
BibTeX
@article{jensen2026-322d13ed,
author = {Jensen, T. D. and Le Guen, Y. and Talozzi, L. and Yang, S. and Gorzynski, J. and Pena-Tauber, A. and Stewart, I. and Ferrasse and others},
title = {{Long-read genome sequencing and multi-omics in aging and neurodegeneration}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.1101/2025.10.10.25337775},
url = {https://doi.org/10.1101/2025.10.10.25337775}
}
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