Project 1: Early Life Stress, DNA Methylation, and Disparities in Obesity across Generations

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)，但将心理社会压力与 人们对健康差距仍然知之甚少。同样，多层次保护因素在多大程度上 (例如，来自个人、人际和社区领域)缓解早期生活压力对 健康结果和潜在的生物学机制尚不清楚。这项提案将调查 假设早期生活压力(20岁之前)会产生DNA甲基化特征，从而导致 与肥胖相关的结果中的健康差异并可代代相传，但可能 被来自个人、人际和社区领域的保护性因素缓解。要实现 为了实现这个项目的目标，我们将利用现有的纵向研究--伯明翰青少年暴力 这项研究收集了关于各种早期生活应激源和保护措施的前瞻性、多信息者数据 阿拉巴马州伯明翰的500多人(78%是黑人，22%是白人，50%是女性)的因素， 纵向平均年龄为11岁、13岁和19岁。该项目将对400名 这一群体的年轻人(平均年龄为26岁)及其200名后代(0至5岁)。它将涉及一项 综合评估肥胖和相关生物标志物(血压、糖化血红蛋白、 炎症标志物)；肥胖和早期生活应激史的评估 以及收集和分析年轻成年人及其后代的唾液DNA。 合并后的数据将用于1)识别与早期DNA甲基化相关的变异 青壮年的生活压力和肥胖；2)确定多层次的保护因素，以减轻 早期生活压力与DNA甲基化和肥胖的关系；以及3)表征 哪些与应激相关的DNA甲基化模式代代相传，并对后代有贡献 肥胖。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 这可能解释了种族健康差异及其在世代之间的传播，以及多层次的 保护性因素可能会中断生物上根深蒂固的逆境的持续 几代人。更好地了解这些过程可能会导致表观遗传生物标记物的开发 对于疾病的早期诊断，识别有成人疾病风险的易感个体的能力，以及 制定新的预防和治疗措施，以缩小健康差距。

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), but the biological mechanisms linking psychosocial stress with health disparities 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 (before age 20) produces DNA methylation profiles that contribute to health disparities in obesity-related outcomes and are transmitted across generations, but can be mitigated by protective factors from individual, interpersonal, and community domains. To achieve the goals of this project, we will capitalize on an existing longitudinal study, the Birmingham Youth Violence Study, which collected prospective, multi-informant data on a variety of early life stressors and protective factors in over 500 individuals (78% Black, 22% White, 50% female) in Birmingham, Alabama, longitudinally at average ages 11, 13 and 19. This project will conduct a follow up assessment on 400 young adults from this cohort (average age 26) and 200 of their offspring (ages 0 to 5). It will involve a comprehensive evaluation of obesity and related biomarkers (blood pressure, glycated hemoglobin, inflammation markers) in the young adults; assessment of obesity and history of early life stress in the offspring; and collection and analyses of salivary DNA from both the young adults and their offspring. The combined data will be used to 1) identify DNA methylation variations that are associated with early life stress and obesity in young adulthood; 2) identify multi-level protective factors that attenuate the associations of early life stress with DNA methylation and obesity; and 3) characterize the extent to which stress-related DNA methylation patterns transmit across generations and contribute to offspring obesity. The findings of this study will provide novel insights into stress-related epigenetic mechanisms that may explain racial health disparities and their transmission across generations, as well as multi-level protective factors that may interrupt the perpetuation of biologically embedded adversity across generations. Better understanding of these processes 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.