POPULATION STRUCTURE OF GENETIC VARIATION IN PREGNANCY

妊娠期遗传变异的人口结构

• 批准号: 7707391
• 负责人: CHARLES SING
• 金额: $ 14.25万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707391
• 关键词: African American; Architecture; Child; Clinical; Collaborations; Complex; DNA; Ensure; Environment; Environmental Risk Factor; Evaluation; Exposure to; Fetus; Gene Frequency; Genes; Genetic; Genetic Epistasis; Genetic Models; Genetic Variation; Genotype; Goals; Haplotypes; High Prevalence; Hispanics; Incidence; Individual; Individual Differences; Length; Maternal and Child Health; Measures; Medical; Mexican; Modeling; Mothers; Neurosecretory Systems; Not Hispanic or Latino; Outcome; Pathway interactions; Physiological; Population; Pregnancy; Premature Birth; Prematurity of fetus; Prevalence; Program Research Project Grants; Rate; Relative (related person); Research; Risk; Sampling; Site; Standards of Weights and Measures; Statistical Models; United States; Variant; abstracting; fetal; gene environment interaction; gene interaction; population genetic structure; racial and ethnic; trait

ABSTRACT OF RESEARCH PLAN Premature birth is recognized as the most significant problem in maternal-child health in the United States. The underlying genetic and environmental factors that contribute to spontaneous preterm birth are poorly understood due to the complex interactions that exist between the mother and fetus to ensure pregnancy continues to term and to the difficulty in applying standard statistical models to study these integrated pathways. This Program Project grant will identify the genetic and environmental factors that contribute in a multifactorial manner to preterm birth, and model the gene, environment and maternal-fetal interactions that may contribute to risk of prematurity. The broad goals of Project II are to model the contribution of genetic and environmental factors that explain inter-individual differences in measures of the maternal-placental-fetal (MPF) neuroendocrine pathway and in prematurity, incorporating maternal-fetal genotype interaction, gene-gene interaction (epistasis), gene-environment interaction and environment-environment interaction. Project II will utilize the phenotypic and clinical measures obtained by the Clinical Core B on 1,200 mother-child pairs, together with the genotypic information on the same individuals typed for multiple SNPs in 16 MPF-related genes collected by the Genotyping Core C. These goals will be accomplished by. 1) establishing for each of the three racial/ethnic populations which variable DNA sites in the mother and fetus, and environmental factors, statistically explain interindividual variation in measures of the MPF neuroendocrine pathway and prematurity (AIM 1), 2) establishing which combination of the variable DNA sites and environmental factors identified in AIM 1 statistically explain interindividual variation in prematurity-related outcomes beyond that predicted by measures of the MPF neuroendocrine pathway (via unmeasured intermediate physiological traits) separately in each racial/ethnic strata (AIM 2) and 3) using the genetic and environmental variables identified in AIM 1, model the genetic architecture of preterm birth incorporating maternal-fetal genotype interaction, gene-gene interaction (indicative of epistasis or non-additivity), gene-environment interaction and environment-environment interaction (AIM 3).

研究计划摘要 在美国，早产被认为是母婴健康中最严重的问题。这个 导致自然早产的潜在遗传和环境因素很少 由于母亲和胎儿之间存在确保怀孕的复杂相互作用而被理解 继续使用标准统计模型来研究这些综合途径的困难。 该计划项目赠款将确定在多因素中起作用的遗传和环境因素 早产的方式，并对可能有助于早产的基因、环境和母婴相互作用进行建模 要冒早产的风险。项目二的广泛目标是模拟遗传和环境的贡献 解释母体-胎盘-胎儿(MPF)神经内分泌测量个体间差异的因素 途径和在早产儿中，包括母婴基因互作、基因-基因互作 (上位性)、基因-环境互作和环境-环境互作。项目II将利用 临床核心B对1,200对母婴进行的表型和临床测量，以及 收集的16个MPF相关基因中多个SNPs分型的同一个体的基因信息 基因分型核心C。这些目标将通过。1)为三个种族/民族中的每一个建立 母亲和胎儿中不同DNA位点的种群，以及环境因素，从统计学上解释了 MPF神经内分泌途径和早产儿测量的个体间差异(AIM 1)，2)建立 在AIM 1中确定的可变DNA位点和环境因素的哪种组合在统计学上可以解释 强积金指标所预测的早产相关结局的个体间差异 不同种族/民族的神经内分泌途径(通过未测量的中间生理特征) 地层(目标2)和3)使用目标1中确定的遗传和环境变量，对基因 包含母婴基因互作、基因-基因互作的早产架构 (表示上位性或非可加性)、基因-环境互作和环境-环境互作 (目标3)。