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

项目 1：早期生活压力、DNA 甲基化和代际肥胖差异

• 批准号: 10161623
• 负责人: Sylvie Mrug
• 金额: $ 17.47万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-22 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161623
• 关键词: Accounting; Adolescence; Adult; Affect; Age; Alabama; Attenuated; Biological; Blood Pressure; Child Rearing; Childhood; Chronic Disease; Collection; Communities; DNA; DNA Methylation; Data; Development; Discrimination; Disease; Early Diagnosis; Epigenetic Process; Evaluation; Exposure to; Family; Female; Generations; Genes; Genotype; Glycosylated Hemoglobin; Goals; Health; Heritability; Human; Individual; Inflammation; Interpersonal Violence; Interruption; Intervention; Interview; Lead; Life; Life Experience; Link; Longitudinal Studies; Measures; Metabolism; Methylation; Minority Groups; Obesity; Outcome; Poverty; Preventive; Process; Psychosocial Stress; Recording of previous events; Regulation; Research; Risk; Role; Salivary; Specialized Center; Stress; Temperament; Time; Variant; Violence; base; behavioral health; cohort; differential expression; disease diagnosis; disorder risk; early experience; early life stress; epigenetic marker; experience; follow up assessment; health disparity; inflammatory marker; informant; insight; intergenerational; methylation pattern; minority health; mortality; neighborhood disadvantage; novel; novel strategies; obesity biomarkers; offspring; offspring obesity; prospective; protective effect; protective factors; pubertal timing; racial disparity; racial health disparity; recruit; response; social cohesion; stressor; transmission process; violence exposure; young adult; youth violence

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.

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.,贫困，人际暴力），但将心理社会压力与 人们对保健方面的差异仍然知之甚少。同样，多层次保护因素在多大程度上 (e.g.,从个人，人际关系和社区领域）减轻早期生活压力的影响， 健康结果和潜在的生物学机制是未知的。该提案将调查 假设早期生活压力（20岁之前）产生DNA甲基化谱， 肥胖相关结果的健康差异，并在代际间传递，但可以 通过个人、人际和社区领域的保护因素减轻。实现 这个项目的目标，我们将利用现有的纵向研究，伯明翰青年暴力 这项研究收集了关于各种早期生活压力源和保护性因素的前瞻性多信息提供者数据。 在亚拉巴马伯明翰的500多名个体（78%黑人，22%白色，50%女性）中， 纵向平均年龄为11岁、13岁和19岁。该项目将对400名 来自这一队列的年轻成年人（平均年龄26岁）和他们的200个后代（年龄0至5岁）。这将涉及一个 肥胖和相关生物标志物（血压，糖化血红蛋白， 炎症标志物）;评估肥胖和早期生活压力的历史， 后代;以及从年轻成年人及其后代收集和分析唾液DNA。 合并的数据将用于1）鉴定与早期乳腺癌相关的DNA甲基化变异， 生活压力和肥胖在年轻的成年人; 2）确定多层次的保护因素，削弱 早期生活压力与DNA甲基化和肥胖的关联;以及3）表征 与压力相关的DNA甲基化模式会代代相传， 肥胖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 这可能解释了种族健康差异及其代际传递，以及多层次的 保护因素，可能会中断永久的生物嵌入逆境， 代更好地理解这些过程可能会导致表观遗传生物标志物的发展 用于疾病的早期诊断，识别成人疾病风险中的易感个体的能力，以及 制定新的预防和治疗措施，减少健康差距。