Iowa CBDRP: Component A BD-STEPS II Core

爱荷华州 CBDRP：组件 A BD-STEPS II 核心

• 批准号: 10421036
• 负责人: KRISTIN CONWAY
• 金额: $ 85万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10421036
• 关键词: Iowa; CBDRP; Component; BD; STEPS

PROJECT SUMMARY In the US, major birth defects affect a delivery every 4½ minutes and the morbidity and mortality of tens of thousands of children annually. An environmental (i.e. non-inherited) exposure or causal gene variant is estimated to explain about one-third of all defects 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 birth defects. Our partnerships with the Iowa Department of Public Health and Iowa Registry for Congenital and Inherited Disorders provide comprehensive and timely surveillance of deliveries to Iowa residents. With these partnerships, we successfully enrolled mothers in the National Birth Defects Prevention Study (NBDPS) and Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) I. Using exposure data and biologic specimens collected, we made substantial contributions to birth defects epidemiology, ranging from methods development to identifying gene-environment interaction effects. Our work has provided critical insights into birth defect etiology and been disseminated in high-impact journals. We propose to expand the work of the Iowa CBDRP through successful participation in the BD-STEPS II. Our overall goal is to identify modifiable maternal exposures in early pregnancy, which may increase the risk for having a pregnancy affected with a major birth defect. We will expertly conduct comprehensive and timely data collection and reporting for the BD- STEPS II using our highly experienced surveillance and research infrastructures. Our proposed research approach is not only consistent with the BD-STEPS II required activities, but expands and innovates the conceived study design (RFA-DD-18-001). We propose to address critical barriers identified in a recent review of the NBDPS to investigate modifiable risk factors for major birth defects. To accomplish this, we will expand the traditional epidemiology approach (used in the NBDPS and BD-STEPS) by integrating a multiomics systems epidemiology approach. Our systems approach is novel in its application to NBDPS and BD-STEPS data. It will use state of the art genomic analysis to lead to improved characterization of the case phenome and improved delineation of pathways that influence birth defect development via the exposome. The expertise of our key personnel and collaborating investigators, along with access to rich exposure and biologic data from independent populations, provides us with unique resources among all CBDRPs, allowing us to successfully implement our systems approach. Additionally, we will continue our leadership role and expand our training of a future generation of birth defect researchers. Along with continuing to train pre-doctoral and postdoctoral scholars, we will now include bachelor’s scholars. Our key personnel, investigators, and scholars will continue our high productivity in disseminating findings from NBDPS and BD-STEPS through peer-reviewed publications. Research findings generated will provide critical insights into modifiable risk factors for major birth defects and be used for family education, treatment improvements, and application of prevention strategies.

项目总结 在美国，严重的出生缺陷每4.5分钟就会影响一次分娩， 每年数以千计的儿童。环境(即非遗传)暴露或因果基因变异是 估计可以解释发生的所有缺陷的大约三分之一。自1996年以来，爱荷华州出生缺陷中心 研究和预防(CBDRP)在重大出生监测和研究中发挥了领导作用 缺陷。我们与爱荷华州公共卫生部和爱荷华州先天性和先天性疾病登记处的合作 遗传性疾病为爱荷华州居民提供全面和及时的分娩监测。有了这些 伙伴关系，我们成功地让母亲参加了国家出生缺陷预防研究(NBDPS)和 评估妊娠暴露(BD-STEPS)的出生缺陷研究I.使用暴露数据和生物 收集的标本，我们在出生缺陷流行病学方面做出了重大贡献，从方法到方法 基因-环境互作效应识别的发展。我们的工作为我们提供了重要的见解 出生缺陷病因学，并在影响较大的期刊上传播。我们建议扩大委员会的工作 爱荷华州CBDRP通过成功参与BD-步骤II。我们的总体目标是确定可修改的 孕妇在怀孕早期暴露，这可能会增加怀孕感染 严重的先天缺陷。我们会专业地为屋宇署进行全面和及时的数据收集和报告- 第二步，使用我们经验丰富的监视和研究基础设施。我们建议的研究 该方法不仅与BD-Steps II所要求的活动一致，而且扩展和创新了 构思研究设计(RFA-DD-18-001)。我们建议解决最近一次审查中确定的关键障碍 以调查重大出生缺陷的可改变的危险因素。为了实现这一目标，我们将扩大 通过整合多组学的传统流行病学方法(用于NBDPS和BD-STEP) 系统流行病学方法。我们的系统方法在NBDPS和BD-STEP中的应用是新颖的 数据。它将使用最先进的基因组分析来改进病例表现组的特征，并 改进了通过曝光组影响出生缺陷发展的途径的描绘。的专业知识 我们的主要人员和合作的调查人员，以及访问丰富的暴露和生物数据 独立的人口，为我们提供了所有CBDRP中独特的资源，使我们能够成功地 实施我们的系统方法。此外，我们将继续发挥领导作用，并扩大我们对 下一代出生缺陷研究人员。同时继续培训博士后和博士后 学者，我们现在包括学士学者。我们的主要人员，调查人员和学者将继续 我们在传播NBDPS和BD调查结果方面的高生产率-通过同行审查的步骤 出版物。所产生的研究结果将为重大出生的可改变风险因素提供关键的见解 并用于家庭教育、改善治疗和预防策略的应用。

项目成果

Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.

• DOI: 10.3390/genes13050816
• 发表时间: 2022-05-03
• 期刊: GENES
• 影响因子: 3.5
• 作者: Justice, Cristina M.;Musolf, Anthony M.;Cuellar, Araceli;Lattanzi, Wanda;Simeonov, Emil;Kaneva, Radka;Paschall, Justin;Cunningham, Michael;Wilkie, Andrew O. M.;Wilson, Alexander F.;Romitti, Paul A.;Boyadjiev, Simeon A.
• 通讯作者: Boyadjiev, Simeon A.

Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.

患有膀胱外翻的亲子三人组的外显子组测序：26 名儿童的研究结果。

• DOI: 10.1002/ajmg.a.62439
• 发表时间: 2021-10
• 期刊: American journal of medical genetics. Part A
• 作者: Pitsava G;Feldkamp ML;Pankratz N;Lane J;Kay DM;Conway KM;Shaw GM;Reefhuis J;Jenkins MM;Almli LM;Olshan AF;Pangilinan F;Brody LC;Sicko RJ;Hobbs CA;Bamshad M;McGoldrick D;Nickerson DA;Finnell RH;Mullikin J;Romitti PA;Mills JL;University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects Prevention Study
• 通讯作者: University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects Prevention Study

Pre-pregnancy dietary arsenic consumption among women in the United States.

美国女性孕前膳食砷摄入量。

• DOI: 10.1002/bdr2.1634
• 发表时间: 2020
• 期刊: Birth defects research
• 影响因子: 2.1
• 作者: Suhl,Jonathan;Conway,KristinM;Rhoads,Anthony;Langlois,PeterH;Feldkamp,MarciaL;Michalski,Adrian;Romitti,PaulA;NationalBirthDefectsPreventionStudy
• 通讯作者: NationalBirthDefectsPreventionStudy

Drinking water disinfection byproducts and risk of orofacial clefts in the National Birth Defects Prevention Study.

国家出生缺陷预防研究中的饮用水消毒副产物和口面部裂风险。

• DOI: 10.1002/bdr2.1348
• 发表时间: 2018
• 期刊: Birth defects research
• 影响因子: 2.1
• 作者: Weyer,Peter;Rhoads,Anthony;Suhl,Jonathan;Luben,ThomasJ;Conway,KristinM;Langlois,PeterH;Shen,Dereck;Liang,Dong;Puzhankara,Soman;Anderka,Marlene;Bell,Erin;Feldkamp,MarciaL;Hoyt,AdrienneT;Mosley,Bridget;Reefhuis,Jennita;Rom
• 通讯作者: Rom

Corrigendum to "BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche" [Bone 112 (July 2018) 58-70].

“非综合征性颅缝早闭中的 BBS9 基因：初级纤毛在缝线成骨生态位异常骨化中的作用”的勘误表 [Bone 112 (2018 年 7 月) 58-70]。

• DOI: 10.1016/j.bone.2019.02.004
• 发表时间: 2019
• 期刊: Bone
• 影响因子: 4.1
• 作者: Barba,Marta;DiPietro,Lorena;Massimi,Luca;Geloso,MariaConcetta;Frassanito,Paolo;Caldarelli,Massimo;Michetti,Fabrizio;DellaLonga,Stefano;Romitti,PaulA;DiRocco,Concezio;Arcovito,Alessandro;Parolini,Ornella;Tamburrini,Gianpiero