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

项目总结 与白人相比，黑人背负着不成比例的慢性病和早期死亡负担。 这些健康差距与黑人经历的高度心理社会压力有关。 (例如，贫穷、人际暴力和歧视)，但生物机制 心理社会压力与健康在一生中的差异仍然鲜为人知。类似地， 多层次保护因素(例如，来自个人、人际和社区)的程度 领域)减轻早期生活应激对健康结果和潜在生物学结果的影响 机制尚不清楚。这项建议将调查早年生活压力产生的假设 慢性疾病早期标志物中导致健康差异的DNA甲基化特征 几个年龄段，这些影响被来自个人，人际， 和社区域。为了实现这个项目的目标，我们将利用现有的 纵向研究，健康的段落，收集了各种前瞻性、多信息者的数据 1000多人(黑人65%，白人35%，女性50%)的早期生活压力源和保护因素 在阿拉巴马州的伯明翰，年龄分别为11岁、13岁、16岁和19岁。 对这一队列中的800名年轻人(平均年龄28岁)及其400名子女(0岁至400岁)的评估 5)。它将涉及对与晚期慢性心脏病相关的心脏代谢指标的全面评估 青壮年疾病(肥胖、高血压、高血糖和炎症)；评估 出生前和出生后应激和后代的保护因素；以及儿童唾液DNA的分析 19岁和28岁的年轻人及其后代。既有馆藏与新馆藏相结合 数据将被用来1)识别与早期生活压力和 三个发育阶段的心脏代谢指标--儿童早期、青春期晚期和 2)研究种族在应激相关DNA甲基化和心脏代谢中的作用 三个发展阶段的指标；以及3)确定多层次的保护因素 修改早期生活压力对三个发育时期DNA甲基化的影响。这个 这项研究的发现将为压力相关的表观遗传机制提供新的见解，这些机制可能 解释生命周期中的种族健康差异，以及可能 中断逆境的生物性嵌入。更好地理解表观遗传学在健康中的作用 差异可能导致表观遗传生物标记物的开发，用于疾病的早期诊断，能力 识别有成人疾病风险的易感人群，并开发新的预防和 将缩小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.