Epidemiology & epigenetics: Maternal diet, DNA methylation, & offspring adiposity

描述(由研究人员提供)：此应用程序涉及挑战领域08，“基因组学”和挑战主题08-AG-105(也称为OD[OBSSR]-102)，“研究关键发育时期个人行为、社会和物理环境以及遗传/表观遗传过程之间相互作用的方法。”数十年的动物生理学实验明确地表明，在发育的早期、可塑性、关键时期的扰动可能会对肥胖、血压和葡萄糖耐受等慢性心脏代谢性疾病的标志物以及寿命本身产生终生的、有时是不可逆转的不利影响。表观遗传学领域最近揭示了这些观察结果背后的一些机制。例如，在黄色刺鼠模型中，受孕前后富含甲基供体的母体饮食会导致一个亚稳定的表观等位基因的DNA甲基化，从而防止后代变得肥胖、糖尿病和癌症易感。然而，在人类群体中，没有研究检查从怀孕早期的母亲饮食通过表观遗传变化到后代表型的途径。这项研究的目标是研究怀孕早期母亲饮食之间的关系，特别是甲基供体摄入量的变化，妊娠早期和晚期母亲血液和脐带血中的全球DNA甲基化，以及3岁和7岁儿童中与肥胖相关的结局。我们将在特点良好的产前队列研究项目Viva中开展这一项目，该项目可能是唯一一项以美国为基础的流行病学研究，其设计特点是解决这些目标：前瞻性收集、验证、早期怀孕饮食信息、孕妇和脐带血样本，以及研究质量的后代心脏代谢表型数据。肥胖、心血管疾病、糖尿病及相关疾病是美国发病率和死亡率的主要原因，它们最早的起源是产前的行为和环境。将表观遗传学数据添加到现有的流行病学研究中，为将动物实验中的知识转化为人类状况以及采取预防性干预措施提供了可能性。考虑到潜在的科学和公共卫生影响，现在是时候让大量资金迅速推动这一领域的发展了，而挑战赠款计划提供了这样做的合适工具。 公共卫生相关性：这项研究的目标是检查怀孕早期母亲的饮食对母体和胎儿DNA甲基化的影响程度，这是一个表观遗传过程；以及DNA甲基化在多大程度上预测3岁和7岁儿童的肥胖和心血管风险因素。这项研究的重要性是双重的。首先是知识获取--将动物实验的结果转化为人类条件的可能性。第二是公共卫生的重要性--优化怀孕早期的母亲饮食可以改善下一代的健康。

DESCRIPTION (provided by investigator): This application addresses Challenge Area 08, "Genomics," and Challenge Topic 08-AG-105 (also OD [OBSSR] - 102), "Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods." Decades of animal physiology experiments unequivocally show that perturbations during early, plastic, critical periods of development can have lifelong, sometimes irreversible adverse impact on markers of chronic cardio- metabolic disease like adiposity, blood pressure and glucose intolerance, and on lifespan itself. The field of epigenetics has recently revealed some of the mechanisms underlying these observations. For example, in the yellow agouti mouse model, a maternal diet rich in methyl donors around conception causes DNA methylation of a metastable epiallele, preventing offspring from becoming fat, diabetic, and cancer-prone. No study in human populations, however, has examined pathways from maternal diet in early pregnancy through epigenetic changes to offspring phenotype. The goals of this study are to examine relationships among maternal diet in early pregnancy, particularly variation in intake of methyl donors, global DNA methylation in maternal blood in early and late pregnancy and in umbilical cord blood, and adiposity-related outcomes in 3- and 7-year-old children. We will carry out this project within the well-characterized pre-birth cohort study Project Viva, which is perhaps the only US-based epidemiologic study with the design features to address these aims: prospectively collected, validated, early pregnancy diet information, maternal and cord blood specimens, and research- quality offspring cardio-metabolic phenotype data. Obesity, cardiovascular disease, diabetes, and related conditions are leading causes of morbidity and mortality in the U.S., and their earliest origins exist in behavior and environment during the prenatal period. Adding epigenetic data to existing epidemiologic studies offers the potential to translate knowledge from animal experiments to the human condition as well as to mount preventive interventions. Given the potential scientific and public health impact, the time has come for an influx of funds to advance this area in significant ways quickly, and the Challenge Grants program provides the right vehicle to do so. PUBLIC HEALTH RELEVANCE: The goals of this study are to examine the extent to which maternal diet in early pregnancy affects methylation of maternal and fetal DNA, an epigenetic process; and the extent to which DNA methylation predicts obesity and cardiovascular risk factors in 3- and 7-year-old children. The importance of this research is two-fold. First is knowledge acquisition--the potential to translate findings from animal experiments to the human condition. Second is public health importance-- optimizing maternal diet in early pregnancy could improve the health of the next generation.