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）：在美国，肥胖症的患病率一直在增加，甚至在婴儿和儿童中也是如此。从儿童期到成年期的肥胖一直被认为是许多慢性疾病（包括许多癌症）的危险因素。尽管致胖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有助于解释为什么一些儿童更容易出现能量摄入过多和随后肥胖的风险增加。尽管据信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，并且与遗传倾向有关。不幸的是，对候选基因、社会环境或其附加影响的研究尚未产生一致的、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期热量摄入和体重的关联，2）识别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出生队列新生儿表观遗传学研究 (NEST) 同步，我们将从其中招募 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，将与调节选定的大脑表达印记基因的序列的 DNA 甲基化谱相关，这些基因已从出生时收集的脐带血淋巴细胞和口腔细胞中表征。将评估约 450,000 个 CpG 的全基因组甲基化谱与行为表型的关系。生成的数据对于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。这些知识对于进一步加深我们对现代肥胖环境中个体差异因素如何导致肥胖脆弱性的理解是必要的。