Iowa CBDRP Comp A: BD-STEPS Core

爱荷华州 CBDRP 比较 A：BD-STEPS 核心

• 批准号: 10765306
• 负责人: KRISTIN CONWAY
• 金额: $ 60万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10765306
• 关键词: Iowa; CBDRP; Comp; BD; STEPS

PROJECT SUMMARY Major birth defects (BDs) affect morbidity and mortality of tens of thousands of newborns annually in the US. Environmental (i.e. non-inherited) exposures or gene variants are estimated to explain about one-third of BDs that occur. Since 1996, the Iowa Center for Birth Defects Research and Prevention (CBDRP) has played a leadership role in surveillance and research of major BDs. Partnerships with the State of Iowa Department of Health and Human Services and Iowa Registry for Congenital and Inherited Disorders have allowed the Iowa CBDRP timely access to comprehensive surveillance data on deliveries to Iowa resident mothers for enrollment in the National Birth Defects Prevention Study and Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS). Using exposure and genomic data collected, the Iowa CBDRP has made substantial contributions to understanding the etiopathogenesis of major BDs, ranging from prevalence estimates to gene- environmental interaction effects, with this work being disseminated in high-impact journals. Findings published support multifactorial inheritance patterns that vary among BDs across system groups and among BD subtypes within a system group. These findings of a heterogeneous etiopathogenesis reinforces the need to continue to investigate major BD phenotypes individually. With this application, the Iowa CBDRP proposes to continue its successful participation in BD-STEPS by timely ascertaining and classifying pregnancies with and without specific major BDs (Aim 1) and developing and evaluating novel modes of exposure data collection (Aim 2). Using data collected, the Iowa CBDRP proposes to expand the traditional epidemiology approach by integrating a multi-omics systems epidemiology approach to more fully investigate risk factors for specific major BDs (Aim 3). The traditional epidemiology approach will be used to examine associations between BD- STEPS exposure data and defects, with international datasets used to conduct confirmation analyses. The systems epidemiology approach will incorporate state-of-the-art genomic studies and machine learning analytics to improve characterization of child phenomes and exposomes and examine gene-environmental interaction effects. Concurrent with the proposed study activities will be training bachelor’s, predoctoral and postdoctoral research scholars to advance the next generation of birth defect researchers (Aim 4). The proposed research and training are not only consistent with BD-STEPS required activities (RFA-DD-23-001) but expands and innovates such activities by improved delineation of exposure pathways and genetic susceptibilities influencing development of specific major BDs. The interdisciplinary expertise of our key personnel and collaborators, along with access to rich exposure and biological data from independent populations, provides the Iowa CBDRP unique resources among all CBDRPs in disseminating novel findings in peer-reviewed publications. Findings generated will provide critical insights into modifiable risk factors for major BDs and be used for family education, treatment improvements, and application of prevention strategies.

项目摘要 重大出生缺陷（BD）影响美国每年数万名新生儿的发病率和死亡率。 据估计，环境（即非遗传性）暴露或基因变异可解释约三分之一的BD 发生的事情。自1996年以来，爱荷华州出生缺陷研究和预防中心（CBDRP）一直在发挥作用， 在监督和研究主要BD方面发挥领导作用。与爱荷华州教育部的伙伴关系 卫生与公众服务部和爱荷华州先天性和遗传性疾病登记处允许爱荷华州 CBDRP及时获得爱荷华州居民母亲分娩的全面监测数据， 入组国家出生缺陷预防研究和出生缺陷研究以评估妊娠 BD-STEPS（BD-STEPS）.利用暴露和收集的基因组数据，爱荷华州CBDRP已经取得了实质性的进展， 有助于了解主要BD的发病机制，从患病率估计到基因， 环境相互作用的影响，这项工作正在高影响力的期刊上传播。的发现刊登 支持多因子继承模式，这些模式在系统组和BD之间各不相同 系统组中的子类型。这些异质性发病机制的发现加强了以下需要： 继续单独研究主要的BD表型。通过这项申请，爱荷华州CBDRP建议： 继续成功参与BD-STEPS，及时确定和分类妊娠， 没有特定的主要BD（目标1），并开发和评估新的暴露数据收集模式 (Aim 2）。利用收集的数据，爱荷华州CBDRP建议通过以下方式扩展传统的流行病学方法 整合多组学系统流行病学方法，以更全面地调查特定 主要BD（目标3）。传统的流行病学方法将被用来检查BD之间的关联- STEPS暴露数据和缺陷，国际数据集用于进行确认分析。的 系统流行病学方法将结合最先进的基因组研究和机器学习 分析，以改善儿童表型和基因组的表征，并检查基因环境 交互作用与拟议的研究活动同时进行的将是培训学士，博士预科和 博士后研究学者推进下一代出生缺陷研究人员（目标4）。的 拟议的研究和培训不仅符合BD-STEPS要求的活动（RFA-DD-23-001） 但通过改善暴露途径和遗传学的描述， 影响特定主要BD发展的敏感性。我们的关键的跨学科专业知识 人员和合作者，沿着访问丰富的暴露和生物数据，从独立的 人口，提供了爱荷华州CBDRP独特的资源，在所有CBDRP传播新的发现， 同行评审的出版物。所产生的结果将为重大疾病的可改变风险因素提供重要见解。 BDs可用于家庭教育、治疗改进和预防策略的应用。