Genetic and Environmental Influences on Childhood Growth

本研究的目的是阐明影响儿童生长发育的遗传和环境因素的作用，特别关注基因与环境的相互作用。这将通过对尼泊尔农村地区的一大群儿童进行纵向研究来实现，那里是寄生虫胃肠道疾病的地方病。拟议的Jiri生长研究是对NIH PA-98-078复杂性状遗传结构的关键规划目标的响应，包括支持新的研究，扩大遗传和环境相互作用的知识，提高基于人群的数据的数量和质量。拟议的Jiri生长研究利用了Jiri蠕虫项目提供的资源，该项目研究了蠕虫感染的遗传易感性。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名男孩和女孩中收集关于生长、成熟、身体组成和健康状况的综合措施，以及关于可能影响研究人口中儿童生长和发育的特定环境因素的信息；目的2是检查生长、成熟、身体组成和健康状况与寄生虫负荷、血液学状况和家庭环境之间的表型关联；目标3是使用现代定量遗传方法来研究生长、成熟、身体组成和健康状况的遗传结构，同时考虑到特定的环境因素作为协变量和/或相互作用项；目的4是使用现代方差成分连锁方法来确定与寄生虫病易感性相关的数量性状位点（qtl）变异对儿童时期生长、成熟、身体组成和健康状况的表型变异的贡献。拟建的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。这项拟议的研究将产生迄今为止收集的关于生长和发育的一系列措施的最大的家族数据库之一。当与将要收集的寄生虫病和家庭环境数据相结合时，拟议的研究将在具有量化GxE相互作用对生长和发育的影响所需的基本成分和统计能力方面是独一无二的。

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.