GENETICS OF ADIPOSE TISSUE DEPOSITION DURING CHILDHOOD

这项研究的目的是阐明积累的遗传学。 并通过应用现代技术对儿童时期的脂肪组织进行图案化 粗放型纵向生长的统计遗传学方法 过去65年从数百个国家收集的发展数据 费尔斯纵向研究中的家庭。超重和不利的 肥胖模式是成人心血管疾病的危险因素，而且两者 脂肪组织的数量和分布具有实质性的遗传性 参与其中。美国约25%的儿童进入 成年后超重，但对其遗传基础几乎一无所知 与生长发育过程中脂肪组织的沉积有关。一个 更清楚地了解脂肪组织沉积的遗传学 童年将有助于发展和应用预防性的 旨在最大限度地减少脂肪组织在 在其他方面保持正常增长的同时保持生长和发育。 解决的具体问题是：男孩有多少钱，以什么速度 女孩在童年时期会增加体脂吗？在童年的时候做爱 脂肪组织沉积的差异出现了？在多大程度上 男孩和女孩脂肪组织沉积的遗传控制 在童年的时候？是否有共同的遗传基础的沉积 不同解剖部位的脂肪组织？童年有脂肪吗？ 组织沉积有主要基因参与，其作用方式是什么？ 儿童时期体重增长的遗传？脂肪是怎么回事？ 儿童时期的组织沉积受总体生长和 成熟？哪些基因与生长的其他方面有关，以及 发育也在脂肪组织的沉积中发挥作用 童年？拟议研究的策略是从简单的 到复杂的统计遗传分析。拟议研究中的步骤 包括：L)估计不同肥胖指标的遗传力 从婴儿期到成年期，2)估计加性遗传和 不同肥胖指标之间的随机环境相关性 从婴儿期到成年期，以确定共享基因的程度 和环境对不同年龄肥胖特征的影响，3)使用 按性别进行的基因分型分析，以检验先天性心脏病发生的遗传学。 儿童时期肥胖症特征中的性别二态，4)使用测量 用基因分析来估计不同基因类型的差异效应 儿童肥胖症的生长激素轴候选基因， 5)确定体重最有可能的遗传方式 童年时期的不同年龄，适合不同年龄的个体生长立方体 肥胖症措施脂肪组织分解过程的措施 将儿童时期的沉积转化为描述大小和强度的参数 肥胖症在生长发育过程中的变化时间， 并检查这些衍生肥胖症生长的遗传基础 参数。这项研究的结果将提供必要的 儿童发育的未来遗传学研究背景 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.