Early Life Stress, DNA Methylation, and Health Disparities across Ages

项目摘要 与白人相比，黑人在慢性病和早期死亡方面承担着不成比例的负担。 这些健康差距与黑人经历的高度心理社会压力有关 (e.g.,贫穷、人际暴力和歧视），但生物机制将 人们对心理社会压力与整个生命周期的健康差异仍然知之甚少。类似地， 多水平保护因素（例如，从个人、人际和社区 领域）减轻早期生活压力对健康结果和潜在生物学的影响。 机制不明。这项建议将调查的假设，早期生活的压力产生 DNA甲基化谱有助于慢性疾病早期标志物的健康差异， 几个年龄组，这些影响是由个人，人际， 和社区领域。为了实现这个项目的目标，我们将利用现有的 纵向研究，健康通道，收集了各种前瞻性，多信息提供者数据， 1，000多人的早期生活压力源和保护因素（65%黑人，35%白色，50%女性） 在亚拉巴马的伯明翰分别是11岁13岁16岁和19岁拟议项目将进行一项后续行动 对来自该队列的800名年轻人（平均年龄28岁）及其400名后代（年龄0至 5）。它将涉及对与晚期慢性心力衰竭相关的心脏代谢指标的综合评价。 疾病（肥胖、高血压、高血糖和炎症）;评估 产前和产后的压力和保护因素的后代;和唾液DNA分析， 19岁和28岁的年轻人以及他们的后代。现有的和新收集的 数据将用于1）鉴定与早期生活压力相关的DNA甲基化变异， 三个发育阶段的心脏代谢指标-幼儿期，青春期后期， 2）研究种族在压力相关的DNA甲基化和心脏代谢中的作用; 三个发展阶段的指标; 3）确定多层次的保护因素， 改变早期生活压力对三个发育阶段DNA甲基化的影响。的 这项研究的发现将为与压力相关的表观遗传机制提供新的见解， 解释整个生命周期中的种族健康差异，以及可能 中断逆境的生物学嵌入。更好地理解表观遗传学在健康中的作用 差异可能导致用于疾病早期诊断的表观遗传生物标志物的发展， 确定成人疾病风险中的易感个体，并开发新的预防和 减少健康差距的治疗措施。

PROJECT SUMMARY Compared to Whites, Blacks carry a disproportionate burden of chronic disease and early mortality. These health disparities have been linked with high levels of psychosocial stress experienced by Blacks (e.g., poverty, interpersonal violence, and discrimination), but the biological mechanisms linking psychosocial stress with health disparities across the lifespan remain poorly understood. Similarly, the extent to which multi-level protective factors (e.g., from individual, interpersonal, and community domains) mitigate the effects of early life stress on health outcomes and underlying biological mechanisms is unknown. This proposal will investigate the hypothesis that early life stress produces DNA methylation profiles that contribute to health disparities in early markers of chronic disease across several age groups, and these effects are modified by protective factors from individual, interpersonal, and community domains. To achieve the goals of this project, we will capitalize on an existing longitudinal study, Healthy Passages, which collected prospective, multi-informant data on a variety of early life stressors and protective factors in over 1,000 individuals (65% Black, 35% White, 50% female) in Birmingham, Alabama at ages 11, 13, 16, and 19. The proposed project will conduct a follow up assessment on 800 young adults from this cohort (average age 28) and 400 of their offspring (ages 0 to 5). It will involve a comprehensive evaluation of cardiometabolic indicators associated with later chronic disease (obesity, hypertension, hyperglycemia, and inflammation) in the young adults; assessment of prenatal and postnatal stress and protective factors in the offspring; and analyses of saliva DNA from the young adults at ages 19 and 28, and their offspring. The combination of existing and newly collected data will be used to 1) identify DNA methylation variations that are associated with early life stress and cardiometabolic indicators across three developmental periods – early childhood, late adolescence, and young adulthood; 2) examine the role of race in stress-related DNA methylation and cardiometabolic indicators across the three developmental periods; and 3) identify multi-level protective factors that modify the effects of early life stress on DNA methylation across the three developmental periods. The findings of this study will provide novel insights into stress-related epigenetic mechanisms that may explain racial health disparities across the lifespan, as well as multi-level protective factors that may interrupt the biological embedding of adversity. Better understanding of the role of epigenetics in health disparities may lead to development of epigenetic biomarkers for early diagnosis of disease, ability to identify susceptible individuals at risk for adult disease, and development of novel preventive and curative measures that would reduce health disparities.