Neighborhood characteristics are robust predictors of overall health and mortality risk for residents. Though there has been some investigation of the role that molecular indicators may play in mediating neighborhood exposures, there has been little effort to incorporate newly developed epigenetic biomarkers into our understanding of neighborhood characteristics and health outcomes. Using 157 participants of the Detroit Neighborhood Health Study with detailed assessments of neighborhood characteristics and genome-wide DNA methylation profiling via the Illumina 450K methylation array, we assessed the relationship between objective neighborhood characteristics and a validated DNA methylation-based epigenetic mortality risk score (eMRS). Associations were adjusted for age, race, sex, ever smoking, ever alcohol usage, education, years spent in neighborhood, and employment. A secondary model additionally adjusted for personal neighborhood perception. We summarized 19 neighborhood quality indicators assessed for participants into 9 principal components which explained over 90% of the variance in the data and served as metrics of objective neighborhood quality exposures. Of the nine principal components utilized for this study, one was strongly associated with the eMRS (β = 0.15; 95% confidence interval = 0.06–0.24; P = 0.002). This principal component (PC7) was most strongly driven by the presence of abandoned cars, poor streets, and non-art graffiti. Models including both PC7 and individual indicators of neighborhood perception indicated that only PC7 and not neighborhood perception impacted the eMRS. When stratified on neighborhood indicators of greenspace, we observed a potentially protective effect of large mature trees as this feature substantially attenuated the observed association. Objective measures of neighborhood disadvantage are significantly associated with an epigenetic predictor of mortality risk, presenting a potential novel avenue by which neighborhood-level exposures may impact health. Associations were independent of an individual’s perception of their neighborhood and attenuated by neighborhood greenspace features. More work should be done to determine molecular risk factors associated with neighborhoods, and potentially protective neighborhood features against adverse molecular effects.

中文翻译：

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全因死亡率的表观遗传预测因子与城市人口邻里劣势的客观衡量标准相关。


社区特征是居民整体健康和死亡风险的有力预测因素。尽管已经对分子指标在调节邻里暴露方面可能发挥的作用进行了一些调查，但几乎没有做出什么努力将新开​​发的表观遗传生物标志物纳入我们对邻里特征和健康结果的理解中。利用底特律社区健康研究的 157 名参与者，通过 Illumina 450K 甲基化阵列对社区特征和全基因组 DNA 甲基化分析进行详细评估，我们评估了客观社区特征与经过验证的基于 DNA 甲基化的表观遗传死亡风险评分 (eMRS) 之间的关系）。关联因素根据年龄、种族、性别、吸烟史、饮酒史、教育程度、在社区生活的年限和就业情况进行了调整。第二个模型还根据个人邻里感知进行了调整。我们将为参与者评估的 19 个社区质量指标总结为 9 个主要组成部分，这解释了数据中 90% 以上的方差，并作为客观社区质量暴露的指标。在本研究使用的九个主要成分中，其中一个与 eMRS 密切相关（β = 0.15；95% 置信区间 = 0.06–0.24；P = 0.002）。这个主要组成部分（PC7）受到废弃汽车、贫困街道和非艺术涂鸦的影响最为强烈。包括 PC7 和邻里感知个体指标的模型表明，只有 PC7 而不是邻里感知影响 eMRS。 当对绿地的邻里指标进行分层时，我们观察到大型成熟树木的潜在保护作用，因为这一特征大大削弱了观察到的关联。邻里劣势的客观测量与死亡风险的表观遗传预测因子显着相关，这提供了邻里水平暴露可能影响健康的潜在新途径。关联独立于个人对其邻里的看法，并因邻里绿地特征而减弱。应该做更多的工作来确定与社区相关的分子风险因素，以及针对不利分子影响的潜在保护性社区特征。