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The Association between Neighborhood Deprivation and DNA Methylation in an Autopsy Cohort
20 Pages Posted: 28 Jul 2023
More...Abstract
Background: Previous research has found that living in a disadvantaged neighborhood is associated with poor health outcomes. Living in disadvantaged neighborhoods may alter inflammation and immune response in the body, which could be reflected in epigenetic mechanisms such as DNA methylation (DNAm).
Methods: We used robust linear regression models to conduct an epigenome-wide association study examining the association between neighborhood deprivation (Area Deprivation Index; ADI), and DNAm in brain tissue from 159 donors enrolled in the Emory Goizueta Alzheimer’s Disease Research Center (Georgia, USA).
Findings: We found one CpG site (cg26514961, gene PLXNC1) significantly associated with ADI after controlling for covariates and multiple testing (p-value=5.0e-8). Effect modification by APOE ε4 was statistically significant for the top ten CpG sites from the EWAS of ADI, indicating that the observed associations between ADI and DNAm were mainly driven by donors who carried at least one APOE ε4 allele. Four of the top ten CpG sites showed a significant concordance between brain tissue and tissues that are easily accessible in living individuals (blood, buccal cells, saliva), including DNAm in cg26514961 (PLXNC1).
Interpretation: Our study identified one CpG site (cg26514961, PLXNC1 gene) that was significantly associated with neighborhood deprivation in brain tissue. PLXNC1 is related to immune response, which may be one biological pathway how neighborhood conditions affect health. The concordance between brain and other tissues for our top CpG sites could make them potential candidates for biomarkers in living individuals.
Funding: This work was supported by the HERCULES Pilot Project via NIEHS P30ES019776 (Huels), the Goizueta Alzheimer’s Disease Research Center: Pilot Grant via NIA P50AG025688 (Huels/Liang), the Rollins School of Public Health Dean’s Pilot and Innovation Grant (Huels) and NIA R01AG079170 (Huels/Wingo).
Declaration of Interest: We have no conflicts of interest to declare.
Ethical Approval: Written consent for brain donation was obtained from next of kin as required under Georgia law. Emory University’s Institutional Review Board approved this study.
Keywords: Neighborhood deprivation, DNA methylation, brain tissue, neuropathology, epigenetics
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