MATERNAL, FETAL & ENVIRONMENTAL CAUSES OF BIRTH DEFECTS

描述：（改编自申请人的描述）当前提案 是基于这样一个前提： 对于许多出生缺陷，只有在“高阶”效应， 基因-环境（GxE）相互作用、基因-基因（GxG）相互作用和母体 基因型效应的评估与更传统的 流行病学和遗传风险因素。此外，最近在 分子遗传学和统计遗传学提供了基础， 研究，解决高阶效应的作用，当这种影响是 根据目前对疾病病因学的理解，调查人员 建议评估GxE相互作用、GxG相互作用和 母体对两组出生缺陷病因的影响：神经管畸形 缺陷和颅骨异常，包括颅缝早闭和非骨性早闭 后斜头畸形（CSINSPP）。这些条件是从其他条件中选择的。 潜在候选人，因为目前对其病因的了解支持 关于高阶效应的多个假设。因此，对于这些 特别是，现在可以开始建立一个多层次的 基因结构的三维蓝图他们将使用国家- 现有技术的基因分型方法，包括高通量阵列技术，以及 采用最先进的统计方法来评估高等教育的作用， 在脊柱裂和CS/NSPP病因学中的顺序效应。

DESCRIPTION: (Adapted from the Applicant's Description) The current proposal is based on the premise that a full understanding of the genetic architecture for many birth defects will only be obtained if "higher-order" effects such as gene-environment (GxE) interactions, gene-gene (GxG) interactions and maternal genotypic effects are evaluated in concert with more traditional epidemiological and genetic risk factors. Moreover, recent advances in molecular and statistical genetics provide a foundation upon which to build studies that address the role of higher-order effects, when such effects are suggested by current understanding of a disease's etiology. The investigators propose to evaluate the role of GxE interactions, GxG interactions and maternal effects in the etiology of two groups of birth defects: neural tube defects and cranial abnormalities including craniosynostosis and nonsynostotic posterior plagiocephaly (CSINSPP). These conditions were selected from other potential candidates because current understanding of their etiologies support multiple hypotheses regarding higher-order effects. Hence, for these conditions in particular, it is now feasible to begin to construct a multi- dimensional blueprint of their genetic architecture. They will use state-of- the-art genotyping methods, including high-throughput array technologies, and employ state-of-the-art statistical approaches to evaluate the role of higher- order effects in the etiology of spina bifida and CS/NSPP.