Dissecting the Genetic Etiology of Preterm Birth in Nulliparous Women

剖析未产妇早产的遗传病因

• 批准号: 8204688
• 负责人: DAVID M. HAAS
• 金额: $ 24.4万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-10 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204688
• 关键词: Accounting; Address; Affect; Biological Markers; Birth Rate; Candidate Disease Gene; Child; Clinical Research; Complex; Complication; DNA; Diagnosis; Diagnostic; Disease; Ensure; Environment; Environmental Risk Factor; Etiology; Family; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genetic screening method; Genomics; Goals; Health Care Costs; Health Expenditures; Healthcare; High Risk Woman; Institution; Intervention; Measures; Newborn Infant; Outcome; Outcome Assessment; Outcomes Research; Physiological; Population Heterogeneity; Pregnancy; Pregnancy Complications; Pregnant Women; Premature Birth; Preventive; Process; Progesterone; Proteomics; Provider; Proxy; Public Health; Publishing; Recording of previous events; Recurrence; Reporting; Research; Research Personnel; Risk; Risk Factors; Sample Size; Sampling; Series; Societies; Specimen; Supplementation; Technology; Testing; Therapeutic; Therapeutic Human Experimentation; United States; Woman; biobank; cost; gene environment interaction; genetic variant; genome wide association study; high risk; improved; innovation; insight; mortality; neonatal morbidity; new technology; novel; pregnant; prevent; public health relevance; success; technological innovation; therapy design

DESCRIPTION (provided by applicant): Despite decades of research, therapeutic discoveries, and technical innovations, the preterm birth rate continues to rise, particularly in nulliparous women. Researchers have sought to identify genes and genetic variants which are risk factors for preterm birth. However, these studies have been hampered by several limitations, including small sample size, reducing the power to detect association, as well as a heterogeneous population that was not limited to nulliparous women. Given the cost and scope of the problem of preterm birth, utilizing new genomic and proteomic technologies to dissect the etiology of preterm birth is imperative. The long-term research goal is to identify a series of DNA polymorphisms and physiologic biomarkers that will improve the understanding of the disease and will identify the subset of nulliparous women at greatest risk for early preterm birth which would allow for targeted intervention or the institution of preventive measures and strategies for this high-risk group. The objective of this application is to join a network of centers dedicated to collecting specimens and information from pregnant nulliparous women. It is expected that a large biorepository will allow for sufficient volume of specimens to test genetic and biomarker hypotheses rigorously, allowing for the discovery of a unique set of genes and biomarkers to serve as diagnostic and treatment targets. The research proposed will conduct a Genomewide association study (GWAS) for the outcome of preterm birth to identify a set of genetic variants associated with preterm birth. In addition, a gene-environment interaction analysis will be performed to control for important environmental influences known to be associated with preterm birth. This proposal is novel in that no prior GWAS has been reported for preterm birth in nulliparous women. Additionally, prior single gene association studies have not controlled for potentially confounding environmental factors in a large, well characterized sample. The research is significant in that preterm birth leads to considerable neonatal morbidity, mortality, and health care costs. It is imperative to develop new strategies to understand this and other pregnancy complications to better prevent, diagnose, and treat conditions such as preterm birth. PUBLIC HEALTH RELEVANCE: The proposal is relevant to public health because it uses novel technologies to better understand the mechanism of disease forthis escalating pregnancy complication which impacts both families and society. The research results from this network of biobanks has potential to dramatically improve providers' ability to prevent, diagnose, and treat many complications of pregnancy in addition to preterm birth.

描述（由申请人提供）：尽管进行了数十年的研究，治疗发现和技术创新，但早产率仍在上升，特别是在无效的女性中。研究人员试图鉴定基因和遗传变异，这是早产的危险因素。但是，这些研究受到了几个局限性的阻碍，包括少量样本量，降低了检测到关联的能力，以及不限于无量子女性的异质人群。考虑到早产问题的成本和范围，使用新的基因组和蛋白质组学技术来解剖早产的病因学是必须的。长期的研究目的是确定一系列DNA多态性和生理生物标志物，将改善对疾病的理解，并将确定对早产早期出生的最大风险的无效妇女的子集，这将允许有针对性的干预或对这个高风险的群体采取预防措施和策略的制度。该应用程序的目的是加入一个专门用于收集孕妇无效妇女的标本和信息的中心网络。可以预期，大型生物座将允许大量的标本严格测试遗传和生物标志物假设，从而发现一组独特的基因和生物标志物可以作为诊断和治疗靶标。拟议的研究将进行全基因组关联研究（GWAS），以实现早产的结果，以确定与早产相关的一组遗传变异。此外，将进行基因环境相互作用分析，以控制已知与早产相关的重要环境影响。该提议是新颖的，因为尚无以前的GWA据报道无效妇女的早产。此外，先前的单基因关联研究尚未控制在大型，表现良好的样本中可能混淆的环境因素。这项研究很重要，因为早产会导致显着的新生儿发病率，死亡率和医疗保健费用。必须制定新的策略来了解这种和其他妊娠并发症，以更好地预防，诊断和治疗早产等疾病。 公共卫生相关性：该提案与公共卫生有关，因为它使用新颖的技术来更好地理解疾病的机制，从而升级了妊娠并发症，这会影响家庭和社会。该生物库网络的研究结果有可能显着提高提供者预防，诊断和治疗许多怀孕并发症的能力，除了早产外。