Early Life Determinants of Obesity in U.S. Urban Low Income Minority Birth Cohort

美国城市低收入少数族裔出生群体的早期肥胖决定因素

• 批准号: 9197671
• 负责人: Bruce Y Lee
• 金额: $ 66.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197671
• 关键词: 10 year old; 2 year old; Address; Adult; Affect; African American; Age; Air Pollution; Animals; Archives; Attention; Biological; Birth; Boston; Cardiovascular Diseases; Censuses; Child; Child health care; Chronic; Chronic Disease; Clinical Data; Complex; Computer Simulation; Computerized Medical Record; Computers; Conceptions; DNA Methylation; Data; Databases; Development; Developmental Process; Diabetes Mellitus; Diet; Disease Marker; Distal; Endocrine Disruptors; Epidemic; Epigenetic Process; Etiology; Exposure to; Folic Acid; Funding; Generations; Genetic Determinism; High Prevalence; Hispanics; Human; Individual; Infant; Infant Health; Insulin Resistance; Intervention; Interview; Lead; Life; Life Cycle Stages; Link; Literature; Location; Longevity; Low income; Malignant Neoplasms; Measures; Mediating; Mental Health; Metabolic Diseases; Metabolic Marker; Metabolic syndrome; Minority; Modeling; Morbidity - disease rate; Mothers; Neighborhoods; Obesity; Outcome; Pathway interactions; Perinatal; Phenotype; Play; Population; Population Heterogeneity; Pregnancy; Probability; Questionnaires; Research; Resources; Risk; Risk Factors; Role; Safety; Sampling; Savings; School-Age Population; Science; System; Testing; Time; Visit; Work; adverse outcome; age group; base; cohort; cost efficient; diabetic; early childhood; epidemiologic data; epigenome; fetal; follow-up; genome-wide; human study; in utero; infancy; innovation; insight; intervention effect; maternal obesity; methylation pattern; models and simulation; mouse model; multidisciplinary; obesity in children; offspring; prenatal; prevent; prospective; public health relevance; pyrosequencing; repository; reproductive; social; virtual

 DESCRIPTION (provided by applicant): Obesity in a young child can not only result in short-term social, psychological, and health effects but also increases the probability to obesity later n life with many possible accompanying chronic conditions such as cardiovascular disease, diabetes, and cancer. Both animal and human studies unequivocally show that perturbations during critical early periods of development can have a life-long, sometimes irreversible, adverse impact on markers of metabolic disease like adiposity and insulin resistance. Obesity's multi-factorial etiology along with developmental processes makes the links between early life factors and childhood obesity a complex system requiring a multi-disciplinary systems approach. Although the potential mechanism is not completely clear, epigenetic mechanisms may play an important role. Our work has shown considerable individual variability of DNA methylation patterns detectable at birth and dynamic in the first two years of life; and that maternal prepregnancy BMI is associated with offspring DNA methylation alterations at birth relevant to chronic disease. However, no study has traced pathways from early life factors through epigenetic changes at birth and early childhood to the development of childhood obesity and related phenotypes among urban low- income African American and Hispanic children who have been disproportionally affected by the obesity epidemic. The first aim of this application is to identify early life risk and protective factors for obesity development. We will investigate a comprehensive array of prenatal and birth to 24-month factors in the development of obesity by leveraging the extensive existing databases and ongoing follow-up of 3,000 Boston Birth Cohort (BBC) children from birth to age 10 years. We will pay particular attention to those potentially important factors that require further study. The second aim is to explore the mediating effect of the epigenome between early life factors and childhood obesity, using existing genome-wide DNA methylation data measured at birth and age 2 years (discovery sample); and replicate important findings by pyrosequencing in an independent sample. The third aim is to develop a Virtual Birth Cohort (VBC) systems dynamics model to represent and help better understand the complex system connecting early life factors with subsequent childhood obesity and determine the key modifiable factors that will most impact the subsequent development of childhood obesity; and test the intervention effects if modifying these factors to different degrees under a variety of scenarios. This highly innovative and efficient approach integrates "real data" from the BBC and then incorporates into a computational simulation model to better understand early life determinants of childhood obesity and epigenetic mechanisms. The VBC also will allow us to explore how findings from the BBC may apply to other locations and circumstances, thus helping generalize our findings. The impact of this project lies in the potential to inform new and sustainable strategies to reduce the burden of childhood obesity during the most critical developmental windows and among the most vulnerable segments of the US population.

 描述（由申请人提供）：幼儿肥胖不仅会导致短期的社会、心理和健康影响，还会增加以后生活中肥胖的可能性，并可能伴随许多慢性疾病，如心血管疾病、糖尿病、动物和人类研究都明确表明，发育早期关键时期的干扰会对肥胖和胰岛素抵抗等代谢疾病的标志物产生终生的、有时是不可逆转的不利影响。病因学和发育过程使得早期生活因素与儿童肥胖之间的联系成为一个复杂的系统，需要多学科系统的方法，尽管潜在的机制尚不完全清楚，但我们的工作表明，表观遗传机制可能发挥着重要的作用。出生时可检测到的 DNA 甲基化模式以及生命头两年的动态变化；母亲孕前 BMI 与后代出生时与慢性疾病相关的 DNA 甲基化改变有关。出生时和该应用程序的首要目的是确定早期生活风险和肥胖发展的保护因素。我们将利用现有的广泛数据库和对 3,000 名波士顿出生队列 (BBC) 儿童（从出生到 10 岁）的持续随访，调查一系列全面的产前和出生至 24 个月内肥胖发展的因素。将特别关注那些需要进一步研究的潜在重要因素，第二个目标是利用现有的出生和2岁时测量的全基因组DNA甲基化数据来探索早期生活因素和儿童肥胖之间的中介作用。第三个目标是开发虚拟出生队列（VBC）系统动力学模型，以表示和帮助更好地理解将早期生活因素与随后的儿童肥胖联系起来的复杂系统。关键这种创新且有效的方法整合了来自儿童肥胖的“真实数据”，并测试了对儿童肥胖随后发展产生重大影响的可修改因素；并测试了在不同程度下修改这些因素的干预效果。 然后将 BBC 纳入计算模拟模型中，以更好地了解儿童肥胖的早期生活决定因素和表观遗传机制。VBC 还将使我们能够探索 BBC 的发现如何适用于其他地点和环境，从而帮助推广我们的发现影响。该项目的重点在于有可能为新的和 可持续战略，以减轻美国人口中最关键的发育窗口期和最脆弱群体的儿童肥胖负担。