Common and Distinct Influences of Prenatal and Postnatal Early-Life Adversity on Epigenomic Trajectories in Mexican American Children

产前和产后早期逆境对墨西哥裔美国儿童表观基因组轨迹的共同和独特影响

• 批准号: 10523031
• 负责人: Andres Cardenas
• 金额: $ 61.77万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-13 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10523031
• 关键词: 14 year old; 18 year old; Acceleration; Address; Adolescence; Affect; Age; Aging; Biological; Biological Markers; Biological Testing; Birth; Blood; California; Candidate Disease Gene; Cell Lineage; Cellular Structures; Child; Childhood; Chronic; Communities; Cues; DNA; DNA Methylation; Data; Development; Disease; Embryonic Development; Environment; Epidemic; Epigenetic Process; Exposure to; Face; Fetal Development; Future; Gene Expression; Genes; Genetic; Genotype; Goals; Health; Hispanic; Household; Immune system; Individual; Inflammatory; Latinx; Life; Longitudinal Studies; Low income; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Mendelian randomization; Metabolic; Methods; Methylation; Mexican Americans; Minority; Minority Groups; Modeling; Morbidity - disease rate; Mothers; Not Hispanic or Latino; Obesity; Obesity Epidemic; Overweight; Pathway interactions; Pattern; Phase; Physiological; Prevalence; Psychosocial Factor; Public Health; Reporting; Research; Risk; Risk Factors; Role; Salinas Valley; Sampling; Social Environment; Statistical Methods; Testing; Tissues; Transcriptional Regulation; Variant; Weather; biological adaptation to stress; biomarker signature; cohort; early childhood; early detection biomarkers; early life adversity; epigenetic marker; epigenome; epigenomics; fetal; field study; health assessment; health disparity; machine learning method; methylation biomarker; methylation pattern; methylome; minority communities; novel; obesity in children; obesity risk; offspring; postnatal; postnatal period; prenatal; prenatal influence; prenatal testing; programs; prospective; psychosocial stressors; racial disparity; response; social; social adversity; stressor; transcriptome sequencing; transcriptomics

PROJECT SUMMARY Childhood obesity is a growing public health epidemic that is disproportionally affecting Hispanic children and associated with morbidity and downstream health disparities. Early-life adversity and childhood psychosocial stressors have been shown to contribute to obesity risk, with stronger effects reported among children growing up in lower-income households. The period of fetal development and early-life are marked by dynamic and rapid changes in fetal DNA methylation programming, epigenetic maturation of immune system-related genes in early- childhood and general physiological development. A poor and adverse social environment in early life has been hypothesized to contribute to epigenomic “weathering” leading to accelerated decline in health, aging and eventual health disparities, including obesity. A leading hypothesis for the origins of health disparities is the biological embedding of adversity on the epigenome due to chronic adversity exposure. While emerging evidence indicates that psychosocial stressors and adversity are associated with epigenetic biomarkers like DNA methylation, significant limitations remain in the field. Namely, most studies to date have been cross-sectional, used candidate gene approaches, not investigated changes or trajectories in epigenetic biomarkers throughout development, or functional consequences in gene expression. The proposed project will leverage data and samples from The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a long- term study of low-income Latinx, predominantly Mexican American, mother-child pairs living in the Salinas Valley of California. We have repeated measurements and samples for DNA methylation analyses at birth, 7, 9, 14 and 18 years in approximately 300 mother-child pairs, genetics, and stabilized RNA for sequencing at 14 years of age. We will investigate both pre- and postnatal early-life adversity measures to 1) determine if adversity measures are associated with blood DNA methylation trajectories and subsequent variation in gene expression; 2) evaluate if adversity measures influence epigenetic aging clocks and biomarkers and their trajectories and if longitudinal changes are prospectively associated with obesity risk; and 3) determine if DNA methylation or epigenetic aging mediate associations with obesity and if an epigenetic adversity score can be constructed from children’s blood methylome. Our study will address critical gaps in the field by testing hypotheses prospectively over 18 years and addressing questions of persistence and embedment of pre- and postnatal adversity. We will test if epigenetic changes influence gene expression with untargeted RNA sequencing at 14 years. We will evaluate if DNA methylation can serve as a reliable biomarker of adversity in early-life and or alternatively if these biomarkers are causal for the relationship between adversity and obesity risk with mediation and mendelian randomization methods. Our approach will yield rigorous data to test the biological embedment of social adversity and its consequences in a Latinx, low-income birth cohort with high obesity prevalence.

项目总结