The Genetics of Infant Growth and Later Obesity

婴儿生长和后期肥胖的遗传学

• 批准号: 7135397
• 负责人: ELLEN W. DEMERATH
• 金额: $ 27.44万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-27 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135397
• 关键词: adipose tissue; body composition; clinical research; developmental genetics; early diagnosis; early experience; family genetics; growth /development; human genetic material tag; human subject; infant human (0-1 year); linkage mapping; longitudinal human study; obesity; phenotype; quantitative trait loci; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Childhood obesity is a serious public health problem in the US and worldwide. Given the relative intractability of obesity once it arises, attention must focus on early prevention, and new evidence indicates that growth rate during the first few years of life is an important early predictor of later obesity risk. Both growth traits and obesity risk are known to be heavily influenced by genetic factors, and there is both theoretical and empirical cause to suspect that these traits share a common genetic pathway related to insulin signaling. Serial data on growth during infancy among related individuals along with later follow-up data are required to fully determine whether or not there is a genetic basis for the association of rapid infant growth with childhood obesity. The proposed collaborative study pairs the serial growth and BMI data from 675 related individuals in the Pels Longitudinal Study, the longest-running study of growth and development in the world, with state-of-the-art statistical and molecular genetic approaches to identify genes involved in infant growth and their possible pleiotropic effects on BMI and the risk of overweight during childhood and adolescence. The study has 5 aims. The goal of Specific Aim 1 is to expand the phenotypic and genotypic dataset already assembled by approximately 50% so as to increase our statistical power to address our hypotheses. The goal of Specific Aim 2 is to document the phenotypic relationships between infant growth (age 0-3 years) and childhood BMI and obesity (from 3-20 years of age), adjusting for mode of infant feeding, gestational age, maternal age, parity, and maternal or paternal size. The goal of Specific Aim 3 is to conduct quantitative genetic analyses to quantify the unique and shared polygenic effects on infant growth rate and later BMI, taking account of sex and age-specific differences, as well as the potential impact of genetic imprinting. The goal of Specific Aim 4 is to identify, through linkage analysis, chromosomal regions (QTL) that influence infant growth, and to assess their potential effects on childhood and adolescent BMI. Finally, the goal of Specific Aim 5 is to examine more closely the QTL already identified in our preliminary studies and the QTL identified in the course of this project by fine-mapping the 1-LOD support intervals surrounding them using additional STRs and a battery of over 3,000 SNPs. Association studies will be conducted to measure the influence of these polymorphisms on early growth traits and childhood/adolescent BMI. With a more thorough understanding of the genetic determinants of growth rate in infancy, and their sustained effects on growth and body weight across the lifespan, effective clinical guidelines on infant growth and feeding, tailored to individual cases, may be easier to design.

描述（由申请人提供）：儿童肥胖是美国和全世界的一个严重的公共卫生问题。鉴于肥胖一旦发生就相对难以处理，注意力必须集中在早期预防上，新的证据表明，生命最初几年的生长速度是以后肥胖风险的重要早期预测因素。众所周知，生长性状和肥胖风险都受到遗传因素的严重影响，并且有理论和经验理由怀疑这些性状共享与胰岛素信号传导相关的共同遗传途径。需要有关个体婴儿期生长的系列数据以及后期的随访数据来充分确定婴儿快速生长与儿童肥胖之间的关联是否存在遗传基础。拟议的合作研究将 Pels 纵向研究（世界上运行时间最长的生长和发育研究）中 675 名相关个体的连续生长和 BMI 数据与最先进的统计和分子遗传学方法配对以识别基因参与婴儿生长及其可能对体重指数和儿童期和青春期超重风险的多效性影响。该研究有 5 个目标。具体目标 1 的目标是将已组装的表型和基因型数据集扩展约 50%，以提高我们的统计能力来解决我们的假设。具体目标 2 的目标是记录婴儿生长（0-3 岁）与儿童 BMI 和肥胖（3-20 岁）之间的表型关系，并根据婴儿喂养方式、胎龄、产妇年龄、胎次，以及母亲或父亲的体型。具体目标 3 的目标是进行定量遗传分析，以量化对婴儿生长率和后期 BMI 的独特且共有的多基因效应，同时考虑性别和年龄特异性差异以及遗传印记的潜在影响。具体目标 4 的目标是通过连锁分析确定影响婴儿生长的染色体区域 (QTL)，并评估其对儿童和青少年 BMI 的潜在影响。最后，具体目标 5 的目标是通过使用额外的 STR 和一系列超过 3,000 个 SNP。将进行关联研究来衡量这些多态性对早期生长特征和儿童/青少年体重指数的影响。随着对婴儿期生长速度的遗传决定因素及其在整个生命周期中对生长和体重的持续影响有了更深入的了解，针对个别病例量身定制的有效的婴儿生长和喂养临床指南可能会更容易设计。