Dissecting the genetic and proteomic risk factors for delirium
Vasilis Raptis, Youngjune Bhak, Timothy I. Cannings, Alasdair M. J. MacLullich, Albert Tenesa. Nature Aging, 2025-11-24
Topic: Risk, prevention and care in population studies
Delirium is an acute change in cognition, common in hospitalized older adults, and associated with high healthcare and human cost; however, delirium's genetic and proteomic background remains poorly understood. Here we conducted a genetic meta-analysis on delirium using multi-ancestry data from the UK Biobank, FinnGen, All of Us Research Program and Michigan Genomics Initiative cohorts (n = 1,059,130; 11,931 cases), yielding the Apolipoprotein E (APOE) gene as a strong delirium risk factor independently of dementia. A multi-trait analysis of delirium with Alzheimer disease identified five delirium genetic risk loci. Plasma proteins associated with up to 16-year incident delirium in UK Biobank (n = 32,652; 541 cases) revealed protein biomarkers implicating brain vulnerability, inflammation and immune response processes. Incorporating proteomic and genetic evidence via Mendelian randomization, colocalization and druggability analyses, we indicate potentially useful drug target proteins for delirium. Combining proteins, APOE-ε4 status and demographics significantly improved incident delirium prediction compared to demographics alone. Our results provide insight into delirium's etiology and may guide further research on clinically relevant biomarkers.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Raptis, V., Bhak, Y., Cannings, T. I., MacLullich, A. M. J., & Tenesa, A. (2025). Dissecting the genetic and proteomic risk factors for delirium. Nature Aging. https://doi.org/10.1038/s43587-025-01018-6
Vancouver
Raptis V, Bhak Y, Cannings TI, MacLullich AMJ, Tenesa A. Dissecting the genetic and proteomic risk factors for delirium. Nature Aging. 2025. doi:10.1038/s43587-025-01018-6. PMID: 41286463.
BibTeX
@article{raptis2025-41286463,
author = {Raptis, Vasilis and Bhak, Youngjune and Cannings, Timothy I. and MacLullich, Alasdair M. J. and Tenesa, Albert},
title = {{Dissecting the genetic and proteomic risk factors for delirium}},
journal = {Nature Aging},
year = {2025},
doi = {10.1038/s43587-025-01018-6},
pmid = {41286463},
url = {https://doi.org/10.1038/s43587-025-01018-6}
}
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.
Key findings
- Delirium is an acute change in cognition, common in hospitalized older adults, and associated with high healthcare and human cost; however, delirium's genetic and proteomic background remains poorly understood.
- Plasma proteins associated with up to 16-year incident delirium in UK Biobank (n = 32,652; 541 cases) revealed protein biomarkers implicating brain vulnerability, inflammation and immune response processes.
- Combining proteins, APOE-ε4 status and demographics significantly improved incident delirium prediction compared to demographics alone.
- Our results provide insight into delirium's etiology and may guide further research on clinically relevant biomarkers.
Why it matters
This genetic meta-analysis found the APOE gene to be a strong delirium risk factor independent of dementia, and identified five delirium genetic risk loci through multi-trait analysis with Alzheimer disease. Combining proteins, APOE-ε4 status, and demographics improved prediction of incident delirium compared with demographics alone.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designmeta-analysis
- Participants1,059,130
- Evidence strengthHigh
How this study scored 66/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 1,059,130 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 | A review of other studies — randomisation is not credited here |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Albert Tenesa: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Edinburgh: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41286463) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
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).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
In the news
1 news article on alzhub's news page cites this paper.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also in Genetics
214 studies in the library are filed under Genetics with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Genetics hub.