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球的严重公共卫生问题。鉴于肥胖一旦出现的相对棘手性，人们就必须关注早期预防，而新的证据表明，生命的头几年的增长率是后来肥胖风险的重要早期预测指标。已知生长特征和肥胖风险都受到遗传因素的严重影响，并且有理论和经验原因怀疑这些特征具有与胰岛素信号传导相关的常见遗传途径。需要完全确定婴儿生长与儿童肥胖症的遗传基础是否存在遗传基础，因此相关个体之间有关婴儿期生长的序列数据以及以后的随访数据。拟议的合作研究配对了PELS纵向研究中675个相关个体的串行增长和BMI数据，这是对世界上最长的生长和发展研究，以及最先进的统计和分子遗传学方法，以鉴定鉴定出涉及婴儿成长的基因及其对BMI的可能性影响和对BMI的风险和不匹配的风险。该研究有5个目标。特定目标1的目的是扩大已经组装约50％的表型和基因型数据集，以增加我们的统计能力以解决我们的假设。特定目标2的目的是记录婴儿生长（0-3岁）与儿童BMI和肥胖（从3-20岁起）之间的表型关系，调整婴儿喂养，胎龄，产妇年龄，平等和母亲或母亲或父亲大小的婴儿喂养模式。特定目标3的目的是进行定量的遗传分析，以量化对婴儿生长速率和后来的BMI的独特和共享多基因作用，考虑到性别和特定年龄的差异，以及遗传印迹的潜在影响。特定目标4的目的是通过连锁分析，鉴定影响婴儿生长的染色体区域（QTL），并评估其对童年和青少年BMI的潜在影响。最后，特定目标5的目的是更仔细地检查我们的初步研究中已经确定的QTL，以及在本项目过程中确定的QTL，通过罚款使用其他STR和3,000多个SNP的电池围绕它们围绕它们的1-LOD支撑间隔。将进行关联研究，以衡量这些多态性对早期生长特征和儿童/青少年BMI的影响。通过对婴儿期生长速率的遗传决定因素有了更透彻的了解，及其对整个寿命的生长和体重的持续影响，对婴儿生长和针对个体病例量身定制的有效临床指南可能更容易设计。