The New England Family Study: Fifty Year Post-Perinatal Follow-Up for Life Course

新英格兰家庭研究：围产后五十年生命历程随访

• 批准号: 7860152
• 负责人: STEPHEN L BUKA
• 金额: $ 71.59万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7860152
• 关键词: 8 year old; Accounting; Adipocytes; Adult; Affect; Age; Aging; Aging-Related Process; Animals; Area; Atherosclerosis; Biological; Biological Assay; Biological Markers; Biopsy; Birth Weight; Blood; Blood Pressure; Calcium; Cardiovascular Diseases; Cells; Characteristics; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical assessments; Collection; Communities; Complement; Coronary artery; DEXA; DNA; DNA Methylation; Data; Data Sources; Databases; Development; Diabetes Mellitus; Disease; Disease Outcome; Distress; Early treatment; Economics; Elderly; Environment; Environmental Risk Factor; Epigenetic Process; Family; Family Study; Fathers; Fatty acid glycerol esters; Fetal Growth Retardation; Fetus; Funding; Future; Future Generations; Gene Expression; Goals; Grant; Growth; Health; Health behavior; Hydrocortisone; Impaired cognition; Knowledge; Learning; Life; Life Cycle Stages; Lipids; Literature; Lumbar Regions; Massachusetts; Measures; Mental Health; Methylation; Mothers; New England; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Occupations; Outcome; Participant; Pathology; Pattern; Perinatal; Phenotype; Placental Insufficiency; Pregnancy; Prevention; Process; Protocols documentation; Public Health; Recruitment Activity; Research; Research Personnel; Resources; Rhode Island; Risk; Risk Factors; Role; Running; Sampling; Scanning; Serum; Services; Siblings; Socioeconomic Status; Source; Time; Tissues; Umbilical cord structure; Visceral; X-Ray Computed Tomography; age related; cardiovascular risk factor; cognitive function; cohort; coronary artery calcification; depressive symptoms; early childhood; experience; fasting glucose; fetal; follow-up; hazard; healthy aging; innovation; interest; maternal cigarette smoking; maternal serum; maternal stress; middle age; neglect; obesity in children; postnatal; prenatal; prevent; programs; prospective; public health relevance; social; socioeconomics; subcutaneous; success; waist circumference

DESCRIPTION (provided by applicant): Little is known regarding how conditions during pregnancy and early life may impact epigenetic alterations and aging processes that could subsequently manifest in midlife as atherosclerosis, type 2 diabetes, adiposity and cognitive decline. In particular, there are sizeable and important knowledge gaps regarding associations of prenatal conditions (e.g. intrauterine growth restriction, maternal serum cortisol levels, maternal smoking and socioeconomic adversity) with epigenetic processes (often measured as DNA methylation) that could alter gene expression and disease outcomes. Our goal is to assess aging processes in 3000 of the Collaborative Perinatal Project (CPP) participants born in 1959-1966 who had detailed prenatal assessments, biosample collection and phenotypic assessments during the first 8 years of life. Specific analytic objectives include: (a) to investigate if DNA methylation in subcutaneous adipocytes is associated with measures of adiposity derived from DEXA scans, CT lumbar region scans (to assess visceral fat), waist circumference and BMI; (b) to identify whether prenatal conditions are associated with adiposity and relevant DNA methylation patterns; (c) to evaluate whether DNA methylation in umbilical cord serum is associated with adiposity at ages 0, 4, 7 years and middle age; (d) to investigate whether prenatal conditions are associated with adiposity-related DNA methylation in umbilical cord serum. The study will recruit 3000 CPP participants from Rhode Island and Massachusetts. Sibling sets discordant for intrauterine growth restriction will be oversampled, with a goal of obtaining 500 sibling sets. Clinical assessments include adiposity, atherosclerosis (coronary artery calcium CT scans), cognitive function, diabetes (fasting glucose), and cardiovascular risk factors (e.g. lipids). Subcutaneous adipocyte biopsies and buccal cell collection will be performed. Maternal cortisol levels during pregnancy (approximately 50 years ago) will be measured from banked serum samples. Umbilical cord serum DNA and adipocyte DNA will be obtained using established protocols, and run through deep sequencing DNA methylation assays as biomarkers of epigenetic characteristics. The analytic approach will include a locus-by- locus analysis for each 26,486 autosomal CpG, assessing the association of average methylation with a) adiposity, and b) prenatal/early life risk conditions, correcting for false discovery rate. Within-sibling analyses will be performed to account for shared family and environment as potential confounders. This study offers to provide innovative information to advance understanding of how epigenetic processes are involved in aging, and how perinatal and early life factors may be important determinants of aging. It is one of the very few data sources available worldwide regarding prenatal, early life and middle-age determinants of health. This study offers potential to make major inroads towards understanding modifiable determinants of aging across the lifecourse, beginning during prenatal and early years of life. This could serve to expand the complement of public health strategies that may enhance healthy aging and prevent disease outcomes. PUBLIC HEALTH RELEVANCE: The search for modifiable influences on healthy aging and aging-related disease has led to considerable interest in the potential health impact of conditions during pregnancy and early childhood (e.g. intrauterine grown restriction, maternal smoking, maternal stress during pregnancy, economic distress, maternal cognitive function, childhood cognitive function, childhood blood pressure, childhood body growth and obesity, childhood neglect and maternal mental health). Such information may contribute to critical and effective new alternatives to enhance healthy aging and prevent later disease, by public health interventions early in life. This project will add to the scientific understanding of biological mechanisms by which prenatal and early life factors may influence health, including the potential discovery of biomarkers as targets for treatment and prevention efforts. Overall, this study is one of the very few available sources of prenatal, early life and middle-aged health determinants and health outcomes worldwide, and offers the potential to make major inroads in more fully understanding prenatal and early life determinants of health.

描述（由申请人提供）：关于怀孕和早期生命中的状况如何影响表观遗传改变和衰老过程，随后可能在中年表现为动脉粥样硬化，2型糖尿病，肥胖和认知能力下降。特别是，关于产前疾病的关联（例如，宫内生长限制，母血清皮质醇水平，孕妇吸烟和社会经济逆境）与表观遗传过程（通常以DNA甲基化的衡量），存在较大且重要的知识差距。我们的目标是评估1959 - 1966年出生的3000个协作围产期项目（CPP）参与者的老化过程，他们在生命的前8年中详细介绍了产前评估，生物样品收集和表型评估。特定的分析目标包括：（a）研究皮下脂肪细胞中的DNA甲基化是否与从DEXA扫描，CT腰部区域扫描（评估内脏脂肪），腰围和BMI得出的脂肪度量有关； （b）确定产前条件是否与肥胖和相关的DNA甲基化模式相关； （c）评估脐带血清中的DNA甲基化是否与0、4、7、7岁和中年的肥胖有关； （d）研究产前条件是否与脐带血清中与脂肪相关的DNA甲基化有关。该研究将招募来自罗德岛和马萨诸塞州的3000名CPP参与者。兄弟姐妹对宫内生长限制的不一致将被过采样，目的是获得500个同级套件。临床评估包括肥胖，动脉粥样硬化（冠状动脉钙CT扫描），认知功能，糖尿病（空腹葡萄糖）和心血管危险因素（例如脂质）。将进行皮下脂肪细胞活检和颊细胞收集。怀孕期间（大约50年前）的孕产妇皮质醇水平将从库存的血清样品中测量。脐带血清DNA和脂肪细胞DNA将使用已建立的方案获得，并通过深层测序DNA甲基化测定作为表观遗传特征的生物标志物。分析方法将包括对每个26,486个常染色体CPG进行逐个基因座分析，评估平均甲基化与a）肥胖的平均甲基化关系，b）产前/早期生活风险条件，以纠正错误发现率。将进行兄弟姐妹分析，以说明作为潜在的混杂因素共享的家庭和环境。这项研究提供了创新信息，以提高对表观遗传过程如何参与衰老的了解，以及围产期和早期生命因素如何成为衰老的重要决定因素。它是全球范围内有关卫生产前，早期和中年决定因素的少数数据来源之一。这项研究提供了潜力，可以使大大了解整个生命的衰老的可修改决定因素，从产前和生命的早期开始。这可能有助于扩大公共卫生策略的补充，这些策略可以增强健康的衰老并预防疾病的结果。 公共卫生相关性：寻找对健康衰老和与衰老相关的疾病的可修改影响导致对妊娠和幼儿期病​​情的潜在健康影响的浓厚兴趣（例如，宫内限制，孕产妇吸烟，孕妇的孕妇压力，经济困扰期间的孕产妇压力，经济困扰，孕妇认知功能，儿童认知能力，儿童脑体育锻炼，儿童体育锻炼，儿童身体健康，儿童的锻炼，儿童，儿童。这种信息可能有助于重要有效的新替代方法，以增强健康的衰老并通过公共卫生的早期开发措施来增强健康的衰老并预防后来的疾病。该项目将增加对产前和早期生命因素可能影响健康的生物学机制的科学理解，包括潜在发现生物标志物作为治疗和预防工作的目标。总体而言，这项研究是全球产前，早期生活和中年健康决定因素和健康成果的极少数可用来源之一，并提供了使人们更充分了解健康和早期生活决定因素的潜力。