Topic: Amyloid, tau and blood-test diagnosis
Brain iron accumulation is well established in Alzheimers disease (AD), but whether the two share a genetic basis remains unclear. Here, we performed genome-wide association analyses of brain iron across six iron-rich brain regions, quantified via quantitative susceptibility mapping (QSM) in 38,142 UK Biobank participants. Genetic pleiotropic overlap, genetic correlation and genomic structural equation modelling were used to identify shared genetic architecture between brain iron and risk of AD, and bidirectional Mendelian randomisation was used to test for causal relationships. We identified 116 independent genome-wide significant loci associated with brain iron (r2<0.1; p <5 x 10-8) and validated these signals in an independent cohort using polygenic scores, which explained between 8.9% and 25.4% of variance in regional iron. Genetic pleiotropy and correlation analyses revealed that brain iron and AD share a polygenic basis extending well beyond the canonical APOE locus. This shared liability is specific to basal ganglia structures relevant to cognition, specifically, iron deposition across the caudate nucleus, putamen, and globus pallidus loaded onto a single latent factor that correlated significantly with AD (rg = 0.13, P = 0.019). Multivariate genome-wide association analysis of the shared liability factor between AD and brain iron revealed 27 independent genome-wide significant loci implicating genes that modulate neuroimmune function. Mendelian randomisation provided no evidence of a causal effect in either direction. In summary, we identified region-specific shared genetic liability between brain iron and AD, and a putative neuroimmune mechanism underlying it.
Key findings
- We identified 116 independent genome-wide significant loci associated with brain iron (r2<0.1; p <5 x 10-8) and validated these signals in an independent cohort using polygenic scores, which explained between 8.9% and 25.4% of variance in regional iron.
- Genetic pleiotropy and correlation analyses revealed that brain iron and AD share a polygenic basis extending well beyond the canonical APOE locus.
- This shared liability is specific to basal ganglia structures relevant to cognition, specifically, iron deposition across the caudate nucleus, putamen, and globus pallidus loaded onto a single latent factor that correlated significantly with AD (rg = 0.13, P = 0.019).
- Multivariate genome-wide association analysis of the shared liability factor between AD and brain iron revealed 27 independent genome-wide significant loci implicating genes that modulate neuroimmune function.
Why it matters
This genetic study found that brain iron deposition and Alzheimer's disease share a polygenic basis, especially in basal ganglia structures. It identifies shared genetic factors but does not test any treatment, cure, or prevention.
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Study details
- Effect size8.9%; 25.4%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 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, 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 25 of the 94 points we could judge it on, which is 27 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 Michelle K. Lupton: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | The University of Queensland: institution h-index 1,516 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 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 | 25 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 25 of the 94 points we could judge it on is 27 out of 100. |
| Total | 27 / 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
Rahman, M. R., Xia, Y., Raniga, P., Fazlollahi, A., Islam, T., Dhruva, A., et al. (2026). Shared genetic architecture between brain iron deposition and Alzheimer's disease. medRxiv (preprint). https://doi.org/10.64898/2026.09.07.26362470
Vancouver
Rahman MR, Xia Y, Raniga P, Fazlollahi A, Islam T, Dhruva A, et al. Shared genetic architecture between brain iron deposition and Alzheimer's disease. medRxiv (preprint). 2026. doi:10.64898/2026.09.07.26362470.
BibTeX
@article{rahman2026-260cf6f2,
author = {Rahman, M. R. and Xia, Y. and Raniga, P. and Fazlollahi, A. and Islam, T. and Dhruva, A. and Ong, J.-S. and MacGregor and others},
title = {{Shared genetic architecture between brain iron deposition and Alzheimer's disease}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.07.26362470},
url = {https://doi.org/10.64898/2026.09.07.26362470}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.