Epigenetic influence on early childhood self-regulation capacities and obesity

表观遗传对幼儿自我调节能力和肥胖的影响

基本信息

批准号：
8210246
负责人：
Bernard F Fuemmeler
金额：
$ 23.55万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8210246
关键词：
Aberrant DNA Methylation Adult Affect Age Attention Behavioral Birth Body mass index Brain Candidate Disease Gene Cells Child Childhood Chronic Disease Cohort Studies Collecting Cell Complex DNA Methylation Data Development Diet Eating Behavior Energy Intake Enrollment Environment Environmental Risk Factor Epigenetic Process Event Failure Food Gametogenesis Gene Expression Genes Genetic Genetic Predisposition to Disease Goals H19 gene Health IGF2 gene Impulsivity Individual Individual Differences Infant Informal Social Control Knowledge Lead Life Light Literature Lymphocyte Malignant Neoplasms Measures Methylation Mothers Newborn Infant Nucleic Acid Regulatory Sequences Nursery Schools Nutrient Obesity Outcome Parenting behavior Parents Participant Pathway interactions Personality Phenotype Physical activity Play Population Prevalence Prevention Prevention strategy Problem behavior Process Proteins Psychopathology Questionnaires Recruitment Activity Regulation Reporting Research Risk Risk Factors Role Satiation Symptoms Testing Umbilical Cord Blood Variant Weight Weight Gain Work addiction aged cohort early childhood eating in absence of hunger genome-wide human disease imprint methyl group neurodevelopment novel obesity in children obesity risk prenatal response skills social teacher treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The prevalence of obesity, even in infants and children, has been increasing in the US. Obesity through childhood and into adulthood is a consistently identified risk factor for a number of chronic diseases, including many cancers. Although the obesiogenic environment is often cited as a key determinate for early childhood obesity, children differ in their vulnerability to the environment. Research on self-regulation capacities may shed light on why some children are more susceptible to an increased risk for excess energy intake and subsequent obesity. Although the self-regulatory components believed to influence risk for early childhood obesity could themselves be influenced by socio-environmental factors (e.g., parenting), there is growing evidence that they are heritable and have associations with genetic predisposition. Unfortunately, studies of candidate genes, the socio-environment or their additive affects have not produced consistent robust findings. Epigenetic mechanisms could be underlying self regulation capacities that influence health outcomes. The objective here is to: 1) determine the association that self-regulation capacities have on early childhood caloric intake and weight, and 2) identify epigenetic marks associated with these self-regulation phenotypes. This preschool study will synchronize with a newly established birth cohort, Newborn Epigenetic STudy (NEST), from which we will recruit a subset of 400 mothers and their children between the ages of 3 and 5. Data on self-regulation capacities will be collected from parent report questionnaires. Indicators of self-regulatory ability such as attention, impulse regulation, and inhibitory control will be associated with DNA methylation profiles at sequences regulating select brain-expressed imprinted genes that have been characterized from cord blood lymphocytes and buccal cells collected at birth. Genome-wide methylation profiles for ~450,000 CpG will be evaluated in relations to behavioral phenotypes. The data generated will be of high scientific value to our understanding of the basic mechanisms underlying the development of self-regulation relevant to adverse health outcomes. Such knowledge is necessary to further advance our understanding of how individual difference factors contribute to vulnerability to obesity in our modern obesiogenic environment. PUBLIC HEALTH RELEVANCE: Self-regulation failures, such as impulsivity, could make some children vulnerable to obesity. A better understanding of the types of self-regulation failures relevant to childhood obesity, as well as the underlying basic mechanism leading to these self-regulation failures could enhance prevention and treatment efforts. This study will clarify the association that self-regulation capacities have with childhood obesity as well as determine the degree to which epigenetic changes acquired prenatally are associated with the development of these self-regulatory capabilities. Knowledge generated from this study will contribute to our understanding of basic mechanisms of self-regulation and its influence on early childhood obesity.

描述（由申请人提供）：在美国，即使在婴儿和儿童中，肥胖症的患病率也在增加。肥胖至童年至成年是多种慢性疾病（包括许多癌症）的始终确定的危险因素。尽管肥胖环境通常被认为是对幼儿肥胖症的关键确定，但儿童对环境的脆弱性有所不同。关于自我调节能力的研究可能会阐明为什么有些儿童更容易受到过多能量摄入和随后肥胖的风险的影响。尽管被认为会影响儿童肥胖风险的自我调节成分本身可能受到社会环境因素（例如育儿）的影响，但越来越多的证据表明它们是可遗传的，并且与遗传倾向有关联。不幸的是，对候选基因，社会环境或其累加影响的研究并未产生一致的健壮发现。表观遗传机制可能是影响健康结果的自我调节能力。这里的目的是：1）确定自我调节能力对幼儿热量摄入和体重的关联，以及2）确定与这些自我调节表型相关的表观遗传标记。这项学龄前的研究将与新成立的出生队列，新生儿表观遗传学研究（NEST）同步，我们将从该研究中招募400个母亲及其3岁之间的400个母亲的子集。将从父母报告问卷中收集有关自我调节能力的数据。自我调节能力的指标，例如注意力，脉冲调节和抑制性控制，将与调节精选脑表达的刻痕基因的DNA甲基化谱有关，这些基因是从脐带血淋巴细胞和出生时收集的颊细胞中表征的。将在与行为表型的关系中评估〜450,000 CpG的全基因组甲基化谱。生成的数据将对我们对与不良健康结果相关的自我调节发展的基本机制的理解具有很高的科学价值。这种知识是必须进一步促进我们对个人差异因素如何导致在现代肥胖环境中脆弱性的理解所必需的。公共卫生相关性：自我调节失败，例如冲动性，可能会使一些孩子容易受到肥胖症的影响。更好地了解与儿童肥胖有关的自我调节失败的类型，以及导致这些自我调节失败的基本机制可以增强预防和治疗工作。这项研究将阐明自我调节能力与儿童肥胖的关联，并确定产前获得的表观遗传变化与这些自我调节能力的发展相关的程度。这项研究产生的知识将有助于我们理解自我调节的基本机制及其对幼儿肥胖的影响。