Epigenetic mechanisms of prenatal environmental stressors and offspring obesity risk

产前环境应激源与后代肥胖风险的表观遗传机制

• 批准号: 10178109
• 负责人: Chantel L. Martin
• 金额: $ 23.24万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10178109
• 关键词: 19 year old; 5 year old; Address; Adult; Adverse event; Age; Air; Air Pollutants; Air Pollution; Award; Behavioral; Biogenesis; Bioinformatics; Biological; Biological Markers; Biological Process; Birth; Birth Weight; Body mass index; Caliber; Censuses; Characteristics; Child; Childhood; Chronic Disease; Cohort Studies; Crime; DNA Methylation; DNA Sequence; Data; Development; Environment; Environmental Exposure; Epigenetic Process; Exposure to; Funding; Genome; Growth; Health; Hispanics; Inequality; Infant; Intervention; Joints; Lead; Life; Life Cycle Stages; Link; Low Birth Weight Infant; Mediator of activation protein; Methylation; Modification; Mothers; Neighborhoods; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Obesity; Outcome; Overweight; Ozone; Pathway interactions; Phase; Positioning Attribute; Poverty; Pregnancy; Process; Public Health; Publications; Research; Research Personnel; Research Training; Risk; Risk Assessment; Risk Factors; Role; Social Environment; Spatial Distribution; Surveys; Toxic Environmental Substances; Training; Umbilical Cord Blood; Vulnerable Populations; Weight Gain; cardiometabolic risk; cardiovascular disorder risk; career; critical period; deprivation; effective intervention; environmental stressor; ethnic minority population; experience; fine particles; follow-up; high risk; improved; infancy; methylation pattern; obesity development; obesity in children; obesity risk; offspring; offspring obesity; overweight child; particle; prenatal; prenatal environmental exposure; prenatal exposure; programs; psychosocial stressors; racial and ethnic; racial and ethnic disparities; racial diversity; residential segregation; segregation; skills; social; violent crime

PROJECT SUMMARY Childhood obesity is a major public health issue in the U.S. with widening racial/ethnic gaps and health consequences across the life course. Inequalities in childhood obesity can be traced to as early as infancy, signifying the prenatal period as potentially a critical window during which differences in environmental exposures may program disparities in offspring obesity risk. Racial/ethnic minorities are disproportionately burdened by adverse environmental conditions, such as neighborhood-level psychosocial stressors and air pollutants, which may act synergistically to impact childhood risk of obesity. Disentangling the effects of prenatal environmental exposures and better understanding the mechanisms through which these exposures influence cardiometabolic risk factors, such as childhood obesity, may lead to improved chronic disease risk assessment and more effective intervention strategies, particularly among vulnerable populations who are more likely to experience adverse environments. Epigenetic mechanisms—changes to the genome that do not modify the DNA sequence—are sensitive to environmental exposures during critical periods and may serve as a putative link to early life disparities in childhood obesity. Previous studies have found that prenatal psychosocial stressors and environmental toxicants are associated with epigenetic modifications, particularly in DNA methylation, and offspring obesity risk, but have not considered the joint effect of these environmental exposures and the underlying biological mediators are not well understood. The proposed research will investigate whether environmental stressors during pregnancy influence offspring obesity risk through modifications in DNA methylation using data from a racially diverse birth cohort study with follow-up into childhood. Through the Pathway to Independence Award, the candidate will gain additional training in environmental exposures, biomarkers and epigenetic mechanisms, bioinformatics, and professional development to successfully transition into an independent research career focused on the early life origins of chronic disease. The skills acquired during the training phase will be used to: 1) Estimate the impact of prenatal neighborhood psychosocial stressors (concentrated poverty, deprivation, racial residential segregation, and violent crime) and air pollution exposure on offspring birth weight, growth trajectory in the first 12 months, and risk of overweight and obesity at 3-5 years of age; 2) Examine the effect of prenatal neighborhood psychosocial stressors and air pollution on offspring DNA methylation marks in umbilical cord blood; and 3) Examine the association between environmental stressor-related DNA methylation marks identified in Aim 2 and risk of childhood overweight or obesity. Completion of the training and research aims will result in scientific presentations and publications, preliminary data to successfully compete for R01 funding, and uniquely position the candidate to make significant contributions to the study of epigenetic profiles relating environmental stressors to childhood obesity risk.

项目摘要 儿童肥胖是美国的一个主要公共卫生问题，种族/民族差距和健康状况正在扩大。 在整个生命过程中的后果。儿童肥胖的不平等可以追溯到婴儿时期， 这意味着产前时期是一个潜在的关键窗口，在此期间， 暴露可能导致后代肥胖风险的差异。种族/族裔少数群体 受到不利环境条件的影响，如邻里心理压力和空气污染。 这些污染物可能协同作用，影响儿童肥胖的风险。解开的影响 产前环境暴露，并更好地了解这些暴露的机制 影响心脏代谢危险因素，如儿童肥胖，可能导致慢性疾病风险的改善 评估和更有效的干预战略，特别是在 更有可能经历不利的环境。表观遗传机制-基因组的变化， 修改DNA序列-在关键时期对环境暴露敏感， 一个假定的联系，以早期生活的差距，儿童肥胖。以前的研究发现，产前 社会心理压力源和环境毒物与表观遗传修饰有关，特别是在 DNA甲基化和后代肥胖的风险，但没有考虑这些环境因素的联合作用 暴露和潜在的生物介质还没有得到很好的理解。拟议的研究将 调查怀孕期间的环境压力因素是否会影响后代肥胖风险， 使用来自种族多样性出生队列研究的数据进行DNA甲基化修饰， 童年.通过独立之路奖，候选人将获得额外的培训， 环境暴露，生物标志物和表观遗传机制，生物信息学和专业 发展成功地过渡到一个独立的研究生涯，专注于早期生命的起源， 慢性病在培训阶段获得的技能将用于：1）估计 产前邻里心理社会压力源（集中贫困，剥夺，种族居住 种族隔离和暴力犯罪）和空气污染暴露对后代出生体重、生长轨迹的影响 12个月，3-5岁时超重和肥胖的风险; 2）检查产前检查的影响 社区心理社会压力和空气污染对子代脐带DNA甲基化的影响 血液;和3）检查环境压力源相关DNA甲基化标记之间的关联 目标2中确定的风险和儿童超重或肥胖的风险。完成培训和研究目标 将产生科学报告和出版物，初步数据，以成功地竞争R 01资金， 和独特的位置的候选人作出重大贡献的研究表观遗传概况有关 环境压力对儿童肥胖风险的影响。