GENETICS OF ADIPOSE TISSUE DEPOSITION DURING CHILDHOOD

这项研究的目的是阐明积累的遗传学 以及儿童时期脂肪组织的形成， 统计遗传学的方法，广泛的纵向增长， 过去65年来，从数百个国家收集的发展数据， Fels纵向研究中的家庭。体重过重， 肥胖模式是成人心血管疾病的危险因素， 脂肪组织数量和分布具有显著的遗传学意义 参与。在美国，大约25%的儿童进入 成年后超重，但实际上对遗传基础一无所知 与生长发育过程中脂肪组织的沉积有关。 一 更清楚地了解脂肪组织沉积的遗传学， 儿童期将有助于预防性药物的开发和应用， 旨在最大限度地减少脂肪组织过度积累的措施， 生长和发育，同时保持正常生长。 具体的问题是：男孩在多大程度上，以什么速度， 而女孩在童年时期就开始发胖 在童年时期， 脂肪组织沉积的差异出现了吗 应担负何种程度的 男孩和女孩脂肪组织沉积的遗传控制 在童年？ 是否有一个共同的遗传基础， 不同解剖部位的脂肪组织 儿童脂肪 组织沉积有主要的基因参与，什么是模式， 儿童时期身体质量增长的遗传？脂肪怎么样 儿童期的组织沉积受整体生长的影响， 成熟？ 哪些基因参与了生长的其他方面， 发育过程中脂肪组织的沉积也发挥作用， 童年？拟议研究的战略是从简单的 到复杂的遗传统计分析。拟议研究的步骤 包括：l）估计不同肥胖指标的遗传率 从婴儿期到青年期，2）估计加性遗传， 不同肥胖指标之间的随机环境相关性 从婴儿期到青年期，以确定共享遗传的程度 和环境对不同年龄肥胖性状的影响，3）使用 按性别进行基因型分析，以检查 儿童期肥胖特征的性二态性，4）使用测量 基因型分析，以估计基因型的差异效应， 生长激素轴中的候选基因座对儿童肥胖性状的影响， 5)确定最可能的身体质量遗传模式， 不同年龄的儿童，6）适合个人的成长立方体系列 肥胖的措施措施分解脂肪组织的过程 沉积在童年时期的参数描述的大小和 在生长和发育过程中肥胖变化的时间， 并检查这些衍生肥胖生长的遗传基础 参数这项研究的结果将提供必要的 未来儿童发育遗传学研究的背景 成人心血管疾病风险。

The goal of this study is to elucidate the genetics of the accumulation and patterning of adipose tissue during childhood by applying modern statistical genetic methods to extensive longitudinal growth and development data collected over the last 65 years from hundreds of families in the Fels Longitudinal Study. Overweight and an unfavorable fat pattern are risk factors for adult cardiovascular disease, and both the amount and distribution of adipose tissue have substantial genetic involvement. Approximately 25% of children in the United States enter adulthood overweight, but virtually nothing is known of the genetic basis to the deposition of adipose tissue during growth and development. A clearer picture of the genetics of adipose tissue deposition during childhood would aid in the development and application of preventive measures aimed at minimizing excess accumulation of adipose tissue during growth and development while otherwise maintaining normal growth. Specific questions addressed are: How much, and at what rates, do boys and girls put on body fat during childhood? When during childhood do sex differences in adipose tissue deposition emerge? What is the extent of genetic control over the deposition of adipose tissue in boys and girls during childhood? Is there a common genetic basis to the deposition of adipose tissue at different anatomical sites? Does childhood adipose tissue deposition have major gene involvement, and what is the mode of inheritance of growth in body mass during childhood? How is adipose tissue deposition during childhood influenced by overall growth and maturation? What genes involved in other aspects of growth and development also play a role in the deposition of adipose tissue during childhood? The strategy of the proposed study is to proceed from simple to complex statistical genetic analyses. Steps in the proposed study include: l) estimate the heritabilities of different adiposity measures from infancy to young adulthood, 2) estimate the additive genetic and random environmental correlations between different adiposity measures from infancy to young adulthood to determine the extent of shared genetic and environmental effects on adiposity traits at different ages, 3) use genotype-by-sex analyses to examine the genetics of the development of sexual dimorphisms in adiposity traits during childhood, 4) use measured genotype analysis to estimate the differential effects of genotypes at candidate loci in the growth hormone axis on childhood adiposity traits, 5) determine the most likely mode of inheritance of body mass at different ages during childhood, 6) fit individual growth cubes to serial measures of adiposity measures to decompose the process of adipose tissue deposition during childhood into parameters describing the magnitude and timing of changes in adiposity over the course of growth and development, and examine the genetic basis to these derived adiposity growth parameters. Findings from this study will provide the necessary background for future genetic studies of the childhood development of adult cardiovascular disease risks.