DNA Methylation Mediates the Association Between Individual and Neighborhood Social Disadvantage and Cardiovascular Risk Factors.
DNA Methylation Mediates the Association Between Individual and Neighborhood Social Disadvantage and Cardiovascular Risk Factors.
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DOI：
10.3389/fcvm.2022.848768
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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作者：
低社会经济地位（SES）和生活在弱势社区与心血管健康状况不佳有关。多条证据表明DNA甲基化与心血管风险因素和社会不利指标有关。然而，有限的研究调查了DNA甲基化在介导个体和社区水平的不利因素与多个心血管危险因素之间的关联中的作用，这些因素存在于大型，多种族，基于人群的队列中。我们研究了在个人层面上的劣势是否（儿童和成人SES）和社区级别（通过人口普查数据评估的社区SES和通过对美学质量、安全性和社会凝聚力的感知评估的社会环境）与11个心血管危险因素相关，包括1个肥胖、糖尿病、血脂和高血压的测量，154名参与者来自动脉粥样硬化的多种族研究（梅萨）。对于显着的关联，我们进行了表观基因组范围内的中介分析，以确定甲基化位点介导的个人/邻里的劣势和心血管危险因素之间的关系，使用JT-Comp方法，评估稀疏的中介作用下的复合零假设。在调整年龄、性别、种族/民族、吸烟、药物使用和祖先遗传主成分的模型中，检测到成年SES与体重指数（BMI）、胰岛素和高密度脂蛋白胆固醇（HDL-C）的相关性，以及FDR q < 0.05时社区社会经济劣势与HDL-C之间的相关性。410个经鉴定与SES-BMI相关的CpG介体富集了与基因表达相关的CpG（表达定量性状甲基化位点，或eQTM），相应的基因在抗原加工和呈递途径中富集。对于BMI以外的心血管危险因素，大多数表观遗传介质在控制BMI后失去了意义。然而，43个甲基化位点显示了在BMI调整后介导邻里社会经济劣势和HDL-C关联的证据。所鉴定的介质富集eQTM，并且相应的基因在炎症和凋亡途径中富集。我们的研究结果支持了DNA甲基化作为个体和社区水平的不利因素与心血管风险因素之间的中介的假设，并揭示了潜在的表观遗传途径。未来的研究需要充分阐明将社会劣势与心血管健康状况不良联系起来的生物学机制。
Low socioeconomic status (SES) and living in a disadvantaged neighborhood are associated with poor cardiovascular health. Multiple lines of evidence have linked DNA methylation to both cardiovascular risk factors and social disadvantage indicators. However, limited research has investigated the role of DNA methylation in mediating the associations of individual- and neighborhood-level disadvantage with multiple cardiovascular risk factors in large, multi-ethnic, population-based cohorts. We examined whether disadvantage at the individual level (childhood and adult SES) and neighborhood level (summary neighborhood SES as assessed by Census data and social environment as assessed by perceptions of aesthetic quality, safety, and social cohesion) were associated with 11 cardiovascular risk factors including measures of obesity, diabetes, lipids, and hypertension in 1,154 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). For significant associations, we conducted epigenome-wide mediation analysis to identify methylation sites mediating the relationship between individual/neighborhood disadvantage and cardiovascular risk factors using the JT-Comp method that assesses sparse mediation effects under a composite null hypothesis. In models adjusting for age, sex, race/ethnicity, smoking, medication use, and genetic principal components of ancestry, epigenetic mediation was detected for the associations of adult SES with body mass index (BMI), insulin, and high-density lipoprotein cholesterol (HDL-C), as well as for the association between neighborhood socioeconomic disadvantage and HDL-C at FDR q < 0.05. The 410 CpG mediators identified for the SES-BMI association were enriched for CpGs associated with gene expression (expression quantitative trait methylation loci, or eQTMs), and corresponding genes were enriched in antigen processing and presentation pathways. For cardiovascular risk factors other than BMI, most of the epigenetic mediators lost significance after controlling for BMI. However, 43 methylation sites showed evidence of mediating the neighborhood socioeconomic disadvantage and HDL-C association after BMI adjustment. The identified mediators were enriched for eQTMs, and corresponding genes were enriched in inflammatory and apoptotic pathways. Our findings support the hypothesis that DNA methylation acts as a mediator between individual- and neighborhood-level disadvantage and cardiovascular risk factors, and shed light on the potential underlying epigenetic pathways. Future studies are needed to fully elucidate the biological mechanisms that link social disadvantage to poor cardiovascular health.
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影响因子：
29
作者：
Deng T;Lyon CJ;Minze LJ;Lin J;Zou J;Liu JZ;Ren Y;Yin Z;Hamilton DJ;Reardon PR;Sherman V;Wang HY;Phillips KJ;Webb P;Wong ST;Wang RF;Hsueh WA
通讯作者：
Hsueh WA
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
4.6
作者：
Brown, Heather;Becker, Frauke;Antwi, Kofi
通讯作者：
Antwi, Kofi
影响因子：
3.9
作者：
Dekkers, Koen F.;Neele, Annette E.;de Winther, Menno P. J.
通讯作者：
de Winther, Menno P. J.
影响因子：
5.2
作者：
Andrade S;Morais T;Sandovici I;Seabra AL;Constância M;Monteiro MP
通讯作者：
Monteiro MP