Elucidating shared genetic signals between type 2 diabetes and three neurodegenerative dementia phenotypes
Ana Luiza Arruda, Archit Singh, Ozvan Bocher, Benjamin Franklin Voight, Andrew P. Morris, Eleftheria Zeggini. Human Genetics and Genomics Advances, 2026-09-02
Topic: Amyloid, tau and blood-test diagnosis
Type 2 diabetes (T2D) and dementia frequently co-occur, yet the biological mechanisms underlying this comorbidity remain incompletely understood. Here, we systematically investigate shared genetic signals between T2D and three forms of neurodegenerative dementia (Alzheimer disease, Lewy body dementia, and sporadic frontotemporal dementia) using large-scale genome-wide association studies of clinically diagnosed individuals. We identify five genomic regions harboring shared association signals between T2D and at least one dementia subtype. Among these, the APOE locus was common to all dementia subtypes, whereas the remaining four loci (GBA, CRY2/PEX16/MAPK8IP1, INO80E, and NSF) were each shared exclusively between T2D and one dementia subtype. Integrating multi-omics data across several disease-relevant tissues and orthogonal lines of functional evidence, we prioritize 26 candidate genes through which these shared genetic loci potentially mediate their effect. Pathway enrichment highlights lipid and lipoprotein regulatory biology as a central shared axis. Mendelian randomization analyses using genetically regulated gene expression in relevant tissues indicate pleiotropic mechanisms with divergent phenotypic consequences. Our findings identify shared genetic loci between T2D and neurodegenerative dementia, revealing systemic metabolic-neurodegenerative trade-offs and highlighting key genes that underpin the comorbidity, providing a framework for improved understanding of age-related multi-morbidity.
Key findings
- Our findings identify shared genetic loci between T2D and neurodegenerative dementia, revealing systemic metabolic-neurodegenerative trade-offs and highlighting key genes that underpin the comorbidity, providing a framework for improved understanding of age-related multi-morbidity.
Why it matters
This genetic study identified shared genetic signals between type 2 diabetes and three forms of neurodegenerative dementia, including the APOE locus common to all dementia subtypes. The findings reveal systemic metabolic-neurodegenerative trade-offs and provide a framework for understanding comorbidity, but do not directly lead to a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Human Genetics and Genomics Advances) |
| Journal's citation record | 0 / 4 | Human Genetics and Genomics Advances: journal h-index 28 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| 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 | 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 | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| 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 | 4 / 4 | Last-listed author Eleftheria Zeggini: h-index 114 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42681870) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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Read the original
- DOI: 10.1016/j.xhgg.2026.100667
- PubMed: 42681870
- Original source →
- Free full text: Human Genetics and Genomics Advances →
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. Check the citation against the original before you use it.
APA 7th
Arruda, A. L., Singh, A., Bocher, O., Voight, B. F., Morris, A. P., & Zeggini, E. (2026). Elucidating shared genetic signals between type 2 diabetes and three neurodegenerative dementia phenotypes. Human Genetics and Genomics Advances. https://doi.org/10.1016/j.xhgg.2026.100667
Vancouver
Arruda AL, Singh A, Bocher O, Voight BF, Morris AP, Zeggini E. Elucidating shared genetic signals between type 2 diabetes and three neurodegenerative dementia phenotypes. Human Genetics and Genomics Advances. 2026. doi:10.1016/j.xhgg.2026.100667. PMID: 42681870.
BibTeX
@article{arruda2026-42681870,
author = {Arruda, Ana Luiza and Singh, Archit and Bocher, Ozvan and Voight, Benjamin Franklin and Morris, Andrew P. and Zeggini, Eleftheria},
title = {{Elucidating shared genetic signals between type 2 diabetes and three neurodegenerative dementia phenotypes}},
journal = {Human Genetics and Genomics Advances},
year = {2026},
doi = {10.1016/j.xhgg.2026.100667},
pmid = {42681870},
url = {https://doi.org/10.1016/j.xhgg.2026.100667}
}
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