Iowa CBDRP Comp A: BD-STEPS Core

项目总结 重大出生缺陷(BDS)影响着美国每年数以万计的新生儿的发病率和死亡率。 据估计，环境(即非遗传)暴露或基因变异可解释大约三分之一的BDS 这是会发生的。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 在主要BDS的监测和研究中发挥领导作用。与爱荷华州政府的伙伴关系 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 参加国家出生缺陷预防研究和出生缺陷研究以评估怀孕 曝光(BD-STEP)。利用收集的暴露和基因组数据，爱荷华州CBDRP已经做出了实质性的 对理解主要BDS的病因做出了贡献，从患病率估计到基因- 环境相互作用效应，这项工作在影响较大的期刊上传播。公布的研究结果 支持在不同BD、不同系统组和不同BD之间变化的多因素继承模式 系统组中的子类型。这些异质性病因的发现强化了 继续个别调查主要的BD表型。通过这项申请，爱荷华州CBDRP建议 继续成功地参与BD-STEPS，及时查明怀孕情况并对其进行分类 没有具体的主要BDS(目标1)，并开发和评价新的曝光数据收集模式 (目标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，更全面地调查特定疾病的危险因素 BDS少校(目标3)。传统的流行病学方法将被用来检查BD与 STEP暴露数据和缺陷，使用国际数据集进行确认分析。这个 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 改善儿童表现组和暴露组的特征并检查基因环境的分析 相互作用的影响。与拟议的学习活动同时进行的还有学士、博士前和 博士后研究学者推进下一代出生缺陷研究人员(目标4)。这个 拟议的研究和培训不仅符合BD-STEPS要求的活动(RFA-DD-23-001) 但通过改进接触途径和基因的描绘，扩展和创新了这种活动 影响特定主要BDS发展的易感性。我们的关键是跨学科的专业知识 人员和合作者，以及从独立机构获得丰富的接触和生物数据 在所有CBDRP中，爱荷华州CBDRP在传播新发现方面提供了独特的资源 同行评议的出版物。所产生的结果将提供对主要 并用于家庭教育、改善治疗和预防策略的应用。

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.