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A Multiethnic Analysis of DNA Methylation Reveals Links Between Alzheimer’s Disease and Metabolic Comorbidities
Landon B, Abraham Daniel A, Fischer T, Phillips NR, Barber RC, Reynolds AW, The Health and Aging Brain Study: Health Disparities (HABS-HD) Study Team.. medRxiv, 2026-10-07
Topic: Genetics and APOE
Background Alzheimer’s disease (AD) is the leading contributor to dementia burden, and the risk of developing it is impacted by a multitude of factors. Among these factors are metabolic conditions like type-2 diabetes (T2D) and metabolic syndrome (MetS), along with ethnicity, which interacts both with AD and the metabolic comorbidities. Previous studies have established associations between methylation patterns at specific CpG sites and risk for AD, T2D and MetS individually, but the underlying etiology that is responsible for interactions between metabolic conditions and AD risk remains unresolved. Objective We aimed to examine methylation patterns among Mexican American (MA) and Non-Hispanic White (NHW) individuals in the context of AD, alongside T2D and MetS, to identify CpG sites associated with disease-specific and interaction-dependent methylation effects related to those comorbidities. Methods DNA methylation data from 551 patients of MA or NHW ancestry who were enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC) were available for analysis. Participants were stratified into groups by AD/T2D status or AD/MetS score and Beta-values from the Illumina MethylationEPIC chip array were obtained for each patient. Differential methylation status was analyzed using the lumi and cate packages in R. Results Five CpG sites had statistically significant differential methylation patterns, including two (cg06322660 and cg25514677) which exhibited significant interactions between AD and T2D status or AD and MetS score respectively, with cg06322660 being significant in the NHW cohort and cg25514677 being significant in the MA cohort. The association at cg25514677 was replicated in an independent MA cohort. Conclusions The two sites associated with interactions between AD and a metabolic condition could explain the influence that those conditions have on the risk for AD and are prime candidates for future study.
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APA 7th
Landon, B., Abraham Daniel, A., Fischer, T., Phillips, N. R., Barber, R. C., & Reynolds, A. W. (2026). A Multiethnic Analysis of DNA Methylation Reveals Links Between Alzheimer’s Disease and Metabolic Comorbidities. medRxiv. https://doi.org/10.64898/2026.10.05.26364777
Vancouver
Landon B, Abraham Daniel A, Fischer T, Phillips NR, Barber RC, Reynolds AW. A Multiethnic Analysis of DNA Methylation Reveals Links Between Alzheimer’s Disease and Metabolic Comorbidities. medRxiv. 2026. doi:10.64898/2026.10.05.26364777.
BibTeX
@article{landon2026-28cb62d3,
author = {Landon, B. and Abraham Daniel, A. and Fischer, T. and Phillips, N. R. and Barber, R. C. and Reynolds, A. W.},
title = {{A Multiethnic Analysis of DNA Methylation Reveals Links Between Alzheimer’s Disease and Metabolic Comorbidities}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.05.26364777},
url = {https://doi.org/10.64898/2026.10.05.26364777}
}
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Key findings
- Objective We aimed to examine methylation patterns among Mexican American (MA) and Non-Hispanic White (NHW) individuals in the context of AD, alongside T2D and MetS, to identify CpG sites associated with disease-specific and interaction-dependent methylation effects related to those comorbidities.
- Results Five CpG sites had statistically significant differential methylation patterns, including two (cg06322660 and cg25514677) which exhibited significant interactions between AD and T2D status or AD and MetS score respectively, with cg06322660 being significant in the NHW cohort and cg25514677 being significant in the MA cohort.
- Conclusions The two sites associated with interactions between AD and a metabolic condition could explain the influence that those conditions have on the risk for AD and are prime candidates for future study.
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Study details
- Participants551
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 32 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported 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 20 of the 62 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| 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 | 2 / 4 | 551 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 | 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 | 20 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 20 of the 62 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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