Genetic and Environmental Influences on Childhood Growth

该研究的目的是阐明遗传和环境因素对儿童生长发育的影响，特别关注基因-环境相互作用。 这将通过对尼泊尔农村的一大批儿童进行纵向研究来实现，尼泊尔农村是寄生虫性胃肠道疾病流行的地方。 拟议的Jiri生长研究是对NIH PA-98-078《复杂性状的遗传结构》中的关键计划目标的回应，包括支持新的研究，扩大遗传和环境相互作用的知识，以及提高基于人口的数据的数量和质量。拟议的Jiri生长研究利用了Jiri蠕虫项目创建的资源，该项目是一项关于蠕虫感染遗传易感性的研究。 拟议的Jiri生长研究有四个具体目标：目标1是定期从大约900名男孩和女孩那里收集一系列全面的生长、成熟、身体成分和健康状况指标，以及有关可能的特定环境因素的信息。影响研究人群中儿童的生长和发育;目的2是检验生长、成熟、身体组成和健康状况的测量与寄生虫负荷、血液学状况和家庭环境的测量之间的表型关联;目的3是利用现代定量遗传学方法来研究生长、成熟、身体组成，考虑到作为协变量和/或相互作用项的具体环境因素的健康状况;目的4是利用现代方差分量连锁分析方法确定数量性状基因座（QTL）的变异贡献与寄生虫病易感性有关，在儿童期生长、成熟、身体组成和健康状况的表型变异。Jiri生长研究的研究人员拥有遗传流行病学、生长学、医学社会学、群体遗传学和体质人类学方面的专业知识。 这项拟议中的研究将产生有史以来收集的最大的家庭数据库之一的生长和发育的系列措施。 当结合寄生虫病和家庭环境数据收集，拟议的研究将是独一无二的，在具有必要的成分和统计能力，需要量化GxE相互作用对生长和发育的影响。

The objective of the proposed study is to elucidate the roles of genetic and environmental factors influencing childhood growth and development, with particular focus on gene-environment interactions. This will be done by establishing a longitudinal study of a large cohort of children in rural Nepal where parasitic gastrointestinal diseases are endemic. The proposed Jiri Growth Study is responsive to key programmatic goals in NIH PA-98-078, Genetic Architecture of Complex Traits, including support of new studies, expanding knowledge of genetic and environmental interactions, and increasing the quantity and quality of population-based data. The proposed Jiri Growth Study leverages resources created by the Jiri Helminth Project, a study of genetic predisposition to helminthic infection. The proposed Jiri Growth Study has four specific aims: Aim 1 is to collect at regular intervals from approximately 900 boys and girls a comprehensive battery of growth, maturation, body composition, and health status measures, as well as information on specific environmental factors that likely impact the growth and development of children in the study population; Aim 2 is to examine phenotypic associations between measures of growth, maturation, body composition and health status, and measures of parasite load, hematological status and household environment; Aim 3 is to use modern quantitative genetic methods to examine the genetic architecture of measures of growth, maturation, body composition, and health status taking into account specific environmental factors as covariates and/or interaction terms; Aim 4 is to use modern variance components linkage methods to determine the contribution of variation in quantitative trait loci (QTLs) linked to parasitic disease susceptibility to phenotypic variation in growth, maturation, body composition, and health status during childhood. Investigators on the proposed Jiri Growth Study have expertise in genetic epidemiology, auxology, medical sociology, population genetics, and physical anthropology. The proposed study will yield one of the largest familial databases ever collected of serial measures of the growth and development. When combined with the parasitic disease and household environment data to be collected, the proposed study will be unique in having the essential ingredients and statistical power needed to quantify GxE interaction effects on growth and development.