A biocultural investigation of epigenetics, gene expression and the intergenerational effects of stress in mothers and neonates

本项目将调查母亲压力、表观遗传标记和婴儿结局之间的关系，这些母亲在怀孕期间经历了极大的压力。这项研究的目的是为了更好地理解表观遗传机制是如何将一代人的压力与下一代基因表达变化和晚年生活结果联系起来的。压力，包括社会心理压力，可能在生理上与后代日后生活结果的变化有关，这一观点是许多关于生长、发育、适应和可塑性的人类学模型的核心。研究结果也将为了解美国日益普遍的压力相关疾病提供潜在的信息。该项目将支持正在进行的生物、文化和医学人类学的国际研究合作和综合研究生培训，为STEM领域中代表性不足的群体的学生提供支持。当今压力最大的环境之一是刚果民主共和国（DRC），战争和战后冲突蹂躏了这个国家20多年。该项目将研究DNA甲基化和基因表达在将母亲的暴力和压力经历转化为母亲及其后代改变的幸福结果中的作用。因此，该项目将促进我们对人类表型可塑性的理解，这是人类学和生物文化研究的中心主题。提出的生物文化方法整合了复杂的人种学、表观基因组学、转录组学和激素数据；已经收集了100对母婴的大量生物样本、产妇压力暴露和新生儿/产妇结局。生物样品将进行DNA甲基化（Illumina MethylationEPIC BeadChip）、基因表达（Agilent SurePrint G3 Human gene expression array）和基于皮质醇的应激测量（ELISA和LC-MS）检测。母亲压力、DNA甲基化、基因表达和新生儿/母亲结局之间的关系将使用多元回归分析进行测试，以更好地了解适应性应激反应的生物学和分子机制。该项目将重点关注与应激过程有关的基因，如HPA轴基因，以及整个基因组，以测试应激的全基因组效应。

This project will investigate relationships among maternal stress, epigenetic markers, and infant outcomes in a sample of mother-infant pairs in which the mothers experienced extreme stress during pregnancy. The goal of the research is to better understand how epigenetic mechanisms may link stress in one generation and changes in gene expression and later-life outcomes in the next generation. The idea that stress, including psychosocial stress, may be related physiologically to changes in an offspring's outcomes later in life is central to many anthropological models of growth, development, adaptation and plasticity. The research findings also will be potentially informative for understanding the increasing prevalence of stress-related disorders in the United States. This project will support ongoing international research collaborations and integrative graduate training in biological, cultural, and medical anthropology for students from groups underrepresented in STEM fields. One of the most stressful environments today is found in the Democratic Republic of Congo (DRC) where war and post-war conflict has ravaged the country for over 20 years. This project will investigate the role of DNA methylation and gene expression in translating experiences of violence and stress in a sample of mothers into altered well-being outcomes for those mothers and their offspring. The project will therefore advance our understanding of human phenotypic plasticity, a central theme in anthropological, biocultural research. The proposed biocultural approach integrates sophisticated ethnographic, epigenomic, transcriptomic, and hormonal data; a wealth of biological samples, maternal stress exposures and neonate/maternal outcomes have already been collected for 100 mother-infant pairs. The biological samples will be assayed for DNA methylation (Illumina MethylationEPIC BeadChip), gene expression (Agilent SurePrint G3 Human Gene Expression array), and cortisol-based stress measures (ELISA and LC-MS). Associations among maternal stress, DNA methylation, gene expression and neonate/maternal outcomes will be tested using multiple regression analyses, to better understand the biological and molecular mechanisms that underlie adaptive responses to stress. The project will focus on genes involved in the stress process, e.g., HPA axis genes, as well as the entire genome to test for genome-wide effects of stress.