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Admixture Mapping of Preterm Birth Genes

早产基因的混合作图

基本信息

批准号：
9093819
负责人：
JEROME F STRAUSS
金额：
$ 25.82万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9093819
关键词：
Admixture African African American Alleles American Birth Birth Rate Candidate Disease Gene Chromosomes, Human, Pair 2 Chromosomes, Human, Pair 21 Data Developed Countries Early Intervention Epigenetic Process European Exclusion Functional disorder Genes Genetic Genetic Markers Genetic Risk Genetic Variation Genome Genotype Goals Healthcare Systems Incidence Individual Knowledge Lead Life Style Link Maps Medical MicroRNAs Neonatal Outcome Pathologic Processes Population Pregnancy Pregnancy Complications Premature Birth Prevention strategy Research Risk Risk Factors Sampling Testing Therapeutic Intervention United States Variant Woman admixture mapping base cost disability exome sequencing expectation experience fetal gene discovery gene environment interaction genetic approach genetic variant health disparity high risk innovation neonate premature preterm premature rupture of membranes prevention clinical trial racial and ethnic disparities transmission process

项目摘要

DESCRIPTION (provided by applicant): Prematurity is one of the most significant medical issues in the United States, costing the American health care system more than 26 billion dollars annually. Moreover, there are significant racial/ethnic disparities in the incidence of preterm birth, with African American women experiencing a disproportionately higher number preterm deliveries compared to European American women. Although the basis for this disparity is likely multi- factorial, there is increasing evidence that genetic variation and gene-environment interaction contribute to the increased risk of preterm birth in African Americans. One approach to elucidate risk factors for the disparity in prematurity, and also to identify targes for therapeutic intervention, is to search for genes that are associated or linked to this outcome. Genetic markers could be used to identify subjects prospectively who might benefit from early interventions. Markers predicting prematurity could also facilitate and reduce the cost of prevention clinical trials through identification of high-risk individuals and exclusion of low ris subjects. Finally, genetic markers could refine understanding of the normal as well as pathologic processes underlying parturition, and lead to innovative medical treatments based on contributing genes. The three Specific Aims proposed in this application represent an objective approach to identifying prematurity genes that contribute to ethnic/racial disparities. The focus will be on preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth and a pregnancy complication that is more frequent in African-Americans. We propose to: 1) Identify loci contributing to PPROM by admixture mapping (AM). This Specific Aim is grounded in the expectation that there are genes that make significant ancestry-specific contributions to risk of PPROM. The hypothesis to be tested is that African ancestry alleles as well as European ancestry alleles admixed into an African ancestry background contribute to risk of PPROM. Stated another way, ancestry and admixture can both make contributions to prematurity. 2) Identify candidate genetic variants lying under AM peaks by exome sequencing. To identify genetic variation in the AM peaks that potentially contribute to PPROM, as well as refine the AM, we will select 50 neonate cases and 50 neonate controls, whose African ancestry is similar (70- 80%), for exome sequencing of chromosomal regions underlying confirmed AM peaks. The hypotheses to be tested are: 1) Loci in the fetal genome on chromosomes 2,8,11,19 and 21 confer increased risk for PPROM~ 2) Loci on chromosome 21 confer risk and protection for PPROM in a population-specific manner~ 3) Risk genetic loci may act through epigenetic mechanisms (microRNAs) to promote PPROM. 3) Test candidate variants for linkage and association with PPROM using the transmission disequilibrium test (TDT). The goal of this Specific Aim is to test candidate genetic variants from regions identified in the feta (neonatal) AM and exome sequencing to determine if they are in association and linkage with PPROM, conferring risk or protection.

描述（由申请人提供）：早产是美国最重要的医疗问题之一，每年花费美国医疗保健系统超过260亿美元。此外，在发病率方面存在显著的种族/族裔差异