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）：关于怀孕期间和早年的状况如何影响表观遗传改变和衰老过程，人们知之甚少，而这些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，关于产前状况（例如宫内生长受限、母亲血清皮质醇水平、母亲吸烟和社会经济逆境）与表观遗传过程（通常以 DNA 甲基化测量）之间的关系存在相当大且重要的知识差距，而表观遗传过程可能会改变基因表达和疾病结果。我们的目标是评估 3000 名 1959-1966 年出生的协作围产期项目 (CPP) 参与者的衰老过程，他们在生命的前 8 年进行了详细的产前评估、生物样本收集和表型评估。具体分析目标包括： (a) 研究皮下脂肪细胞中的 DNA 甲基化是否与 DEXA 扫描、CT 腰部区域扫描（以评估内脏脂肪）、腰围和 BMI 得出的肥胖测量值相关； (b) 确定产前状况是否与肥胖和相关 DNA 甲基化模式有关； (c) 评估脐带血清中的DNA甲基化是否与0、4、7岁和中年的肥胖相关； (d) 研究产前状况是否与脐带血清中肥胖相关的 DNA 甲基化有关。该研究将招募来自罗德岛州和马萨诸塞州的 3000 名 CPP 参与者。与宫内生长受限不一致的兄弟姐妹集将被过度采样，目标是获得 500 个兄弟姐妹集。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（空腹血糖）和心血管危险因素（例如血脂）。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）的母亲皮质醇水平将从储存的血清样本中测量。将使用既定方案获得脐带血清 DNA 和脂肪细胞 DNA，并通过深度测序 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 26,486 个常染色体 CpG 进行逐位点分析，评估平均甲基化与 a) 肥胖和 b) 产前/早期生命风险状况的关联，纠正错误发现率。将进行兄弟姐妹内分析，以将共同的家庭和环境视为潜在的混杂因素。这项研究提供了创新信息，以促进对表观遗传过程如何参与衰老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的理解。它是全球为数不多的关于产前、早期和中年健康决定因素的数据来源之一。这项研究有可能在了解从产前和生命早期开始的整个生命过程中可改变的衰老决定因素方面取得重大进展。这可以扩大公共卫生战略的补充，从而促进健康老龄化和预防疾病结果。 公共卫生相关性：寻找对健康老龄化和老龄相关疾病的可改变影响，引起了人们对怀孕和幼儿期条件（例如宫内生长受限、母亲吸烟、怀孕期间母亲压力、经济困难）的潜在健康影响的极大兴趣。 、母亲认知功能、儿童认知功能、儿童血压、儿童身体生长和肥胖、儿童忽视和母亲心理健康）。这些信息可能有助于通过生命早期的公共卫生干预来提供关键且有效的新替代方案，以促进健康老龄化并预防后期疾病。该项目将增进对产前和生命早期因素可能影响健康的生物机制的科学理解，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，这项研究是全世界为数不多的可用的产前、早期和中年健康决定因素和健康结果来源之一，并有可能在更全面地了解产前和早期健康决定因素方面取得重大进展。