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: 9766397
• 负责人: Chantel L. Martin
• 金额: $ 9.08万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766397
• 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; Childhood Overweight; Chronic Disease; Cohort Studies; Crime; DNA Methylation; DNA Sequence; Data; Data Quality; 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; follow-up; high risk; improved; infancy; methylation pattern; obesity development; obesity in children; obesity risk; offspring; offspring obesity; particle; prenatal; prenatal environmental exposure; prenatal exposure; programs; psychosocial; racial and ethnic; racial and ethnic disparities; racial diversity; segregation; skills; social; stressor; 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.

项目总结