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: 8605888
• 负责人: DAVID M. HAAS
• 金额: $ 19.71万
• 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/8605888
• 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 Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; 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）：尽管经过数十年的研究、治疗发现和技术创新，早产率仍在继续上升，特别是在未经产的妇女中。研究人员试图确定基因和遗传变异是早产的危险因素。然而，这些研究受到了一些限制，包括样本量小，降低了检测关联的能力，以及不限于未经产妇女的异质性人群。鉴于早产问题的成本和范围，利用新的基因组和蛋白质组学技术来剖析早产的病因是势在必行的。长期研究目标是确定一系列DNA多态性和生理生物标志物，以提高对该疾病的认识，并确定早期早产风险最大的未产妇亚组，从而可以针对性地进行干预或制定针对这一高风险群体的预防措施和战略。本申请的目的是加入一个致力于收集未经产孕妇标本和信息的中心网络。预计大型生物储存库将允许足够体积的标本严格测试遗传和生物标志物假设，允许发现一组独特的基因和生物标志物，作为诊断和治疗靶点。这项研究将对早产的结果进行全基因组关联研究（GWAS），以确定一组与早产相关的遗传变异。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。这一建议是新颖的，因为没有先前的GWAS已报告早产的未经产妇女。此外，以前的单基因关联研究没有控制潜在的混杂环境因素在一个大的，充分表征的样品。这项研究的意义在于早产导致相当大的新生儿发病率、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。 公共卫生关系：该提案与公共卫生有关，因为它使用新技术来更好地了解这种不断升级的妊娠并发症的疾病机制，这种并发症影响家庭和社会。来自这个生物库网络的研究结果有可能大大提高供应商预防，诊断和治疗除早产外的许多妊娠并发症的能力。

项目成果

Factors associated with duration of breastfeeding in women giving birth for the first time.

• DOI: 10.1186/s12884-022-05038-7
• 发表时间: 2022-09-22
• 期刊: BMC PREGNANCY AND CHILDBIRTH
• 影响因子: 3.1
• 作者: Haas, David M.;Yang, Ziyi;Parker, Corette B.;Chung, Judith;Parry, Samuel;Grobman, William A.;Mercer, Brian M.;Simhan, Hyagriv N.;Silver, Robert M.;Wapner, Ronald J.;Saade, George R.;Greenland, Philip;Merz, Noel Bairey;Reddy, Uma M.;Pemberton, Victoria L.
• 通讯作者: Pemberton, Victoria L.