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

• 批准号: 8338462
• 负责人: Bernard F Fuemmeler
• 金额: $ 19.63万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8338462
• 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

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.

描述（由申请人提供）：肥胖的患病率，甚至在婴儿和儿童中，在美国一直在增加。儿童期和成年期的肥胖一直被认为是许多慢性疾病（包括许多癌症）的风险因素。虽然致肥环境经常被认为是早期儿童肥胖的关键决定因素，但儿童对环境的易感性不同。对自我调节能力的研究可能会揭示为什么有些儿童更容易受到能量摄入过多和随后肥胖风险增加的影响。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（例如，养育子女）的影响，但越来越多的证据表明，它们是可遗传的，与遗传易感性有关。不幸的是，对候选基因、社会环境或它们的附加影响的研究并没有产生一致的强有力的发现。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幼儿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。这项学前研究将与新建立的新生儿表观遗传研究（NEST）同步进行，我们将从中招募400名年龄在3至5岁之间的母亲及其子女。关于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甲基化谱有关，这些DNA甲基化谱是通过出生时收集的脐带血淋巴细胞和颊细胞来调节选择的脑表达印迹基因的序列。将评估约450,000 CpG的全基因组甲基化谱与行为表型的关系。所产生的数据将对我们理解与不良健康结果相关的自我调节发展的基本机制具有很高的科学价值。这些知识对于我们进一步了解个体差异因素如何在现代致肥环境中导致肥胖的易感性是必要的。