Epigenetic influence on early childhood self-regulation capacities and obesity

描述(申请人提供)：在美国，肥胖症的流行，即使是在婴儿和儿童中，也一直在增加。从童年到成年，肥胖一直是许多慢性病的危险因素，包括许多癌症。尽管顺应环境经常被认为是儿童早期肥胖的关键决定因素，但儿童对环境的脆弱性有所不同。对自我调节能力的研究可能会揭示为什么一些儿童更容易受到过量能量摄入和随后肥胖的风险增加的影响。尽管被认为影响儿童早期肥胖风险的自我调节因素本身可能受到社会环境因素(如育儿方式)的影响，但越来越多的证据表明，这些因素是可遗传的，并与遗传易感性有关。不幸的是，对候选基因、社会环境或其附加影响的研究并没有产生一致的可靠结果。表观遗传机制可能是影响健康结果的潜在自我调节能力。这里的目标是：1)确定自我调节能力与儿童早期卡路里摄入量和体重之间的关联，以及2)确定与这些自我调节表型相关的表观遗传标记。这项学龄前研究将与新建立的出生队列-新生儿表观遗传学研究(Nest)同步进行，我们将从其中招募400名母亲及其3至5岁的孩子。有关自我调节能力的数据将从家长报告问卷中收集。自我调节能力的指标，如注意力、冲动调节和抑制控制，将与DNA甲基化相关，这些序列调节从出生时收集的脐带血淋巴细胞和口腔细胞中提取的特定大脑表达的印记基因。约450,000个CpG的全基因组甲基化情况将根据行为表型进行评估。产生的数据将对我们理解与不良健康后果相关的自我调节发展的基本机制具有很高的科学价值。这些知识对于进一步推进我们对个体差异因素如何在现代顺应环境中导致肥胖易感性的理解是必要的。 与公共健康相关：自律失灵，如冲动，可能会使一些儿童容易患肥胖症。更好地了解与儿童肥胖有关的自我调节失误的类型，以及导致这些自我调节失误的基本机制，可以加强预防和治疗工作。这项研究将阐明自我调节能力与儿童肥胖之间的联系，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。这项研究所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儿童早期肥胖的影响。

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.