POPULATION STRUCTURE OF GENETIC VARIATION IN PREGNANCY

研究计划摘要 早产被认为是美国母婴健康中最严重的问题。的 导致自发性早产的潜在遗传和环境因素很差 由于母亲和胎儿之间存在复杂的相互作用以确保怀孕，因此可以理解 继续术语和应用标准统计模型来研究这些综合路径的困难。 该计划项目赠款将确定促成多因素的遗传和环境因素 早产的方式，并模拟可能有助于早产的基因、环境和母胎相互作用 以免出现早产的风险。项目 II 的总体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 途径和早产儿，结合母体-胎儿基因型相互作用、基因-基因相互作用 （上位性）、基因-环境相互作用和环境-环境相互作用。项目二将利用 临床核心 B 对 1,200 对母子进行的表型和临床测量，以及 同一个体的基因型信息，对 16 个 MPF 相关基因中的多个 SNP 进行分型 基因分型核心 C。这些目标将通过以下方式实现。 1) 为三个种族/族裔中的每一个建立 母体和胎儿 DNA 位点存在变异的人群以及环境因素，从统计学角度解释 MPF 神经内分泌通路测量值的个体差异和早产 (AIM 1), 2) 建立 AIM 1 中确定的可变 DNA 位点和环境因素的组合可以统计解释 早产相关结果的个体差异超出了强积金措施的预测范围 每个种族/民族的神经内分泌途径（通过未测量的中间生理特征）分别 层（AIM 2）和3）使用AIM 1中确定的遗传和环境变量，对遗传进行建模 早产的结构包括母体-胎儿基因型相互作用、基因-基因相互作用 （表示上位性或非相加性），基因-环境相互作用和环境-环境相互作用 （目标 3）。

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).