DATA MANAGEMENT AND STATISTICAL ANALYSIS CORE

研究摘要 早产被认为是美国母婴健康中最重要的问题。的 导致自发性早产的潜在遗传和环境因素并不明显， 由于母亲和胎儿之间存在复杂的相互作用，以确保怀孕， 继续长期和困难的应用标准的统计模型来研究这些综合途径。 这项计划项目赠款将确定遗传和环境因素，有助于在多因素 早产的方式，并模拟基因，环境和母胎相互作用， 早产的风险。项目II的主要目标是模拟遗传和环境因素的贡献， 解释母体-胎盘-胎儿（MPF）神经内分泌指标个体间差异的因素 途径和早产儿，纳入母胎基因型相互作用，基因-基因相互作用 （上位性）、基因-环境互作和环境-环境互作。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 在16个MPF相关基因中对同一个体的多个SNP进行分型的基因型信息， 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 母亲和胎儿中可变DNA位点的人群，以及环境因素，在统计学上解释了 MPF神经内分泌通路和早产（AIM 1）测量的个体间差异，2）建立 AIM 1中确定的可变DNA位点和环境因素的组合在统计学上解释了 早产相关结局的个体间差异超出MPF测量的预测 神经内分泌通路（通过未测量的中间生理特征）分别在每个种族/民族中 层（AIM 2）和3）使用在AIM 1中确定的遗传和环境变量， 结合母胎基因型相互作用、基因-基因相互作用的早产结构 （指示上位性或非加性）、基因-环境互作和环境-环境互作 (AIM 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).