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

Abstract

AbstractBackgroundLiterature 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.MethodThis 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.ResultResults 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.ConclusionThe 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.