Follow-up and Maintenance of the Newborn Epigenetics STudy (NEST) Cohort

项目摘要 包括心血管疾病、代谢疾病和癌症在内的非传染性疾病是 是发达国家的主要死因。据预测，这些疾病也是导致 到2020年发展中国家的死亡率。要遏制这些疾病流行率的上升， 使用生命过程方法更详细地了解其病因。现有数据提前链接 这些成人发病疾病的化学和非化学应激源来自有力的交叉， 部分或回顾性队列研究，或随访时间较短的把握度不足的前瞻性队列。后生 基因的改变是基因对环境做出反应的一种机制， 观察早期压力源和多种常见疾病之间的关联。然而，先前的横截面 回顾性研究缺乏早期生活协变量数据和样本，这将有助于检查 早期生活压力和晚年疾病之间的联系。为了弥补这些知识差距，2005-2011年，我们 开发了包括2000多名妇女的产前新生儿表观遗传学研究（NEST）队列， 他们的后代，直到3-5岁。NEST队列已成为我们小组使用的资源， 确定化学和非化学应激源之间的新联系，以及这些非化学应激源的早期迹象。 传染病，包括心脏代谢功能障碍。这一资源也被用于复制 其他组的新发现，与其他队列合并以提高统计功效，并测试新的 其他人的假设。这个应用程序的首要目标是维护这个资源。这将是 通过留住具有关键技能的训练有素的工作人员来实现，以㈠维持和充实队伍 通过收集更多的数据和样本，（ii）制定和实施质量控制和质量保证 关于现有和将要收集的数据和标本的议定书，以及㈢建立一个全面的网络基础 数据库，以提高我们的能力，数据重用和汇集与其他同伙，以提高统计权力。 直接网络访问还将简化与其他出生队列共享数据的过程，并准备我们的数据 用于连接。我们将跟踪队列，直到11-17岁。这一年龄范围与青春期前后相吻合， 易患非传染性疾病的青春期发展窗口期 调查我们还将把NEST数据与可识别的卫生系统和国营医疗记录联系起来。 完成拟议的研究将导致一个丰富的标本库，质量控制和质量 保证和注释的流行病学和临床数据。这些数据和样本将有助于快速 我们小组的假设检验以及与其他群组的数据共享和联系，以加强统计 动力.有助于我们理解成人发病非传染性疾病发展起源的数据 疾病对于指导公共卫生干预工作至关重要。

Project Summary Non-communicable diseases including cardiovascular diseases, metabolic diseases and cancer are the leading causes of death in developed countries. These diseases are predicted to also be the leading causes of death in developing countries by 2020. Stemming the increase in the prevalence of these diseases will require a more detailed understanding of their etiology using a life course approach. Existing data linking early chemical and non-chemical stressors to these adult-onset diseases derives either from well-powered cross- section or retrospective cohort studies, or under-powered prospective cohorts with short follow-up. Epigenetic alterations—a mechanism by which genes respond to the environment—have been hypothesized to link observed associations between early stressors and multiple common diseases. However, prior cross-sectional and retrospective studies have lacked early life covariate data and specimens that would help to examine the links between early life stressors and later life disease. To address these knowledge gaps, in 2005-2011, we developed the pre-birth Newborn Epigenetics STudy (NEST) cohort comprising more than 2000 women, and followed their offspring until age 3-5 years. The NEST cohort has become a resource used by our group to identify novel associations between chemical and non-chemical stressors, and early signs of these non- communicable diseases, including cardiometabolic dysfunction. This resource has also been used to replicate novel findings by other groups, to pool with other cohorts to enhance statistical power, and to test new hypotheses by others. Our overarching goal for this application is to maintain this resource. This will be accomplished through the retention of trained staff with the critical skills to, (i) maintain and enrich the cohort by collecting additional data and specimens, (ii) develop and implement quality control and quality assurance protocols on existing and to-be-collected data and specimens, and, (iii) establish a comprehensive web-based database to increase our capability for data re-use and pooling with other cohorts to enhance statistical power. Direct web access will also simplify the process of data sharing with other birth cohorts and prepare our data for linkage. We will follow the cohort until age 11-17 years. This age range coincides with peri-puberty and puberty—developmental windows of heightened susceptibility to the non-communicable diseases under investigation. We also will link NEST data with identifiable Health System- and State-run medical records. Completing the proposed study will result in an enriched specimen repository with quality control and quality assurance, and annotated epidemiologic and clinical data. These data and specimens will facilitate rapid hypothesis testing by our group as well as data sharing and linkage with other cohorts to enhance statistical power. Data contributing to our understanding of the developmental origins of adult-onset non-communicable diseases are critical for guiding public health intervention efforts.