Epigenetic influence on early childhood self-regulation capacities and obesity

描述（由申请人提供）：在美国，肥胖症的患病率一直在增加，即使在婴儿和儿童中也是如此。从儿童期到成年期的肥胖一直是许多慢性病（包括许多癌症）的危险因素。虽然致肥胖环境通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增加过量能量摄入和随后肥胖的风险。虽然被认为影响儿童早期肥胖风险的自我调节成分本身可能受到社会环境因素的影响（例如，父母），越来越多的证据表明，他们是遗传的，并与遗传易感性。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强有力的结果。表观遗传机制可能是影响健康结果的潜在自我调节能力。这方面的目标是：1）确定自我调节能力与儿童早期热量摄入和体重的关系，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，我们将招募400名母亲及其3至5岁的孩子。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甲基化谱在序列调节选择脑表达的印记基因，其特征在于从脐带血淋巴细胞和口腔细胞收集在出生时。将评价约450，000个CpG的全基因组甲基化谱与行为表型的关系。所产生的数据将具有很高的科学价值，我们了解的基本机制的发展自我调节相关的不良健康结果。这些知识是必要的，以进一步推进我们的理解，个体差异因素如何有助于在我们的现代obesigenic环境中的肥胖的脆弱性。

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.