Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Aging (Albany NY). 2024 Apr 24;16(8):6694-6716. doi: 10.18632/aging.205764.
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). 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). We found one CpG site (cg26514961, gene ) significantly associated with ADI after controlling for covariates and multiple testing (p-value=5.0e). Effect modification by 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 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 (). Our study identified one CpG site (cg26514961, gene) that was significantly associated with neighborhood deprivation in brain tissue. 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.
先前的研究发现,居住在贫困社区与健康状况不佳有关。生活在贫困社区可能会改变体内的炎症和免疫反应,这可能反映在表观遗传机制中,如 DNA 甲基化(DNAm)。我们使用稳健的线性回归模型进行了全基因组关联研究,以检查社区贫困(区域贫困指数;ADI)与 159 名入组埃默里·戈伊祖塔阿尔茨海默病研究中心(美国佐治亚州)的脑组织中 DNAm 之间的关联。在控制协变量和多重检验后,我们发现一个 CpG 位点(cg26514961,基因)与 ADI 显著相关(p 值=5.0e)。ε4 的效应修饰在 ADI 的 EWAS 的前十个 CpG 位点中具有统计学意义,表明 ADI 与 DNAm 之间观察到的关联主要由携带至少一个 ε4 等位基因的供体驱动。在 ADI 的 EWAS 中,前十个 CpG 位点中有四个与脑组织和在活个体中容易获得的组织(血液、口腔细胞、唾液)中的 DNAm 具有显著一致性,包括 cg26514961 中的 DNAm()。我们的研究确定了一个 CpG 位点(cg26514961,基因),该位点与脑组织中的社区贫困显著相关。与免疫反应有关,这可能是社区条件影响健康的一种生物学途径。我们的顶级 CpG 位点在大脑和其他组织之间的一致性可能使它们成为生活个体中潜在的生物标志物候选物。