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Interaction between DNA methylation and neighborhood disadvantage may impact risk for cognitive decline among Mexican Americans enrolled in the Health and Aging Brain Study – Health Disparities (HABS‐HD) Cohort
Mohammad Housini, Zhengyang Zhou, Amy Kind, Danielle Marie Reid, Ann Abraham Daniel, Talisa K. Silzer, Sid E. O’Bryant, Nicole Phillips et al.. Alzheimer s & Dementia, 2023-12-01
Topic: Brain proteins, microglia and lab models
Abstract Background Literature continues to indicate that social exposome factors such as neighborhood disadvantage, measured by the area deprivation index (ADI), is associated with cognitive decline, total brain volume, hippocampal volume and AD neuropathology. We hypothesize that epigenetic markers are implicated in the effect of neighborhood disadvantage on neurodegenerative biomarkers among Mexican Americans. We used existing Illumina EPIC Methylation chip and ADI data from 32 Mexican American participants enrolled in the Heath & Aging Brain Study ‐ Health Disparities (HABS‐HD) cohort to test whether differentially methylated sites and regions moderate a portion of the effect of ADI on risk for implicated AT(N) biomarkers. Method This study included Mexican American participants with information on DNA methylation, ADI, and Neurofilament Light (NfL), who were part of the Health and Aging Brain Study – Health Disparities (HABS‐HD). We considered 25 targeted epigenetic markers, which were previously identified to be associated with MCI or NfL from our group. We conducted preliminary analysis to assess associations between ADI and NfL using whole data (n = 812), and whether such association is moderated by one of the aforementioned targeted epigenetic markers using data with DNA methylation information (n = 32). Linear regression models were conducted to test the above effects and adjust for covariates. Result Results of the linear regression models showed that ADI was significantly positively associated with NfL among Mexican Americans (p = 0.007) using whole data, but the moderation analysis revealed no significant moderating effects on such association for any of the targeted epigenetic markers. However, one CpG site, cg07413251, showed marginally significant interaction effects with ADI on the association with NfL (p = 0.056). The cg07413251 site maps to a CpG island located at chr3p24.1. The biological implications of differential methylation at this site are unknown and remain under investigation. Conclusion The lack of significant results for moderation effects of the targeted epigenetic markers in our pilot study were likely due to the small sample size. In our future work, we will expand samples size significantly, improving power to better understand the role of disadvantaged neighborhoods in influencing cognitive function. Investigations into other biomarkers are underway.
Key findings
- Abstract Background Literature continues to indicate that social exposome factors such as neighborhood disadvantage, measured by the area deprivation index (ADI), is associated with cognitive decline, total brain volume, hippocampal volume and AD neuropathology.
- We considered 25 targeted epigenetic markers, which were previously identified to be associated with MCI or NfL from our group.
- Result Results of the linear regression models showed that ADI was significantly positively associated with NfL among Mexican Americans (p = 0.007) using whole data, but the moderation analysis revealed no significant moderating effects on such association for any of the targeted epigenetic markers.
- However, one CpG site, cg07413251, showed marginally significant interaction effects with ADI on the association with NfL (p = 0.056).
- Conclusion The lack of significant results for moderation effects of the targeted epigenetic markers in our pilot study were likely due to the small sample size.
Why it matters
In a preliminary analysis of 32 Mexican American participants, researchers tested whether DNA methylation moderates the effect of neighborhood disadvantage on neurodegenerative biomarkers. The small sample size means these findings are early and cannot yet inform treatment, cure, or prevention.
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Study details
- Participants812
- Evidence strengthModerate
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 812 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 5 year(s) since 2023 |
| 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 | 2 / 4 | Last-listed author Gita A. Pathak: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 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 |
| Total | 39 / 100 | — |
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Read the original
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APA 7th
Housini, M., Zhou, Z., Kind, A., Reid, D. M., Daniel, A. A., Silzer, T. K., et al. (2023). Interaction between DNA methylation and neighborhood disadvantage may impact risk for cognitive decline among Mexican Americans enrolled in the Health and Aging Brain Study – Health Disparities (HABS‐HD) Cohort. Alzheimer s & Dementia. https://doi.org/10.1002/alz.080609
Vancouver
Housini M, Zhou Z, Kind A, Reid DM, Daniel AA, Silzer TK, et al. Interaction between DNA methylation and neighborhood disadvantage may impact risk for cognitive decline among Mexican Americans enrolled in the Health and Aging Brain Study – Health Disparities (HABS‐HD) Cohort. Alzheimer s & Dementia. 2023. doi:10.1002/alz.080609.
BibTeX
@article{housini2023-bed5ab2c,
author = {Housini, Mohammad and Zhou, Zhengyang and Kind, Amy and Reid, Danielle Marie and Daniel, Ann Abraham and Silzer, Talisa K. and O’Bryant, Sid E. and Phillips, Nicole and others},
title = {{Interaction between DNA methylation and neighborhood disadvantage may impact risk for cognitive decline among Mexican Americans enrolled in the Health and Aging Brain Study – Health Disparities (HABS‐HD) Cohort}},
journal = {Alzheimer s \& Dementia},
year = {2023},
doi = {10.1002/alz.080609},
url = {https://doi.org/10.1002/alz.080609}
}