Dissecting the Genetic Etiology of Preterm Birth in Nulliparous Women

描述(由申请人提供)：尽管经过了几十年的研究、治疗发现和技术创新，但早产率仍在继续上升，特别是在未分娩的妇女中。研究人员试图确定哪些基因和基因变异是早产的风险因素。然而，这些研究受到几个限制的阻碍，包括样本量小，降低了发现相关性的能力，以及不同的人群并不局限于未分娩的妇女。考虑到早产问题的成本和范围，利用新的基因组和蛋白质组技术来剖析早产的病因势在必行。长期的研究目标是确定一系列DNA多态和生理生物标记物，以提高对疾病的了解，并确定早产风险最大的未分娩妇女亚群，从而为这一高危群体进行有针对性的干预或制定预防措施和战略。这项应用的目标是加入一个中心网络，专门收集怀孕未分娩妇女的标本和信息。预计大型生物信息库将允许足够数量的样本严格测试遗传和生物标记物假说，从而能够发现一组独特的基因和生物标记物作为诊断和治疗目标。这项拟议的研究将对早产的结果进行全基因组关联研究，以确定一组与早产有关的遗传变异。此外，还将进行基因-环境交互作用分析，以控制已知与早产有关的重要环境影响。这一建议是新颖的，因为以前没有关于未分娩妇女早产的报道。此外，先前的单基因关联研究还没有对大样本中潜在的混杂环境因素进行控制。这项研究意义重大，因为早产会导致相当大的新生儿发病率、死亡率和医疗费用。必须开发新的策略来了解这一点和其他妊娠并发症，以便更好地预防、诊断和治疗早产等疾病。 与公共健康相关：该提案与公共健康相关，因为它使用了新技术来更好地了解这种不断升级的怀孕并发症的发病机制，这种并发症对家庭和社会都有影响。来自这个生物库网络的研究结果有可能极大地提高提供者预防、诊断和治疗早产以外的许多妊娠并发症的能力。

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.