GENETIC EPIDEMIOLOGY OF CHILDHOOD OBESITY

肥胖症是一种慢性疾病，患病率很高且不断上升， 身体和精神健康并发症，无法治愈，以及未知的 病因学 最近的科学工作已经确定了多种遗传原因 肥胖的啮齿动物，从而奠定了基础，解开 控制身体脂肪含量的生物途径的复杂网络。 确定导致人类肥胖的遗传因素的首要任务是 从表型良好的生物样本中获取- 具有大量核心家庭的大人口的特点。 人类基因组分析领域的快速发展将提供 改进的技术用于我们的研究。 我们的假设是 肥胖症是一种异质性疾病， 多个遗传位点的等位基因差异，其中一些可能是 啮齿类动物肥胖基因的人类同源物。 我们将继续进行题为“遗传流行病学的研究， 儿童肥胖症”通过执行这些具体目标：1）进行一个 使用多点连锁分析的全基因组搜索和候选 通过招募新研究，使用TDT分析进行基因关联研究 既往接受过减肥手术的患者人群及其 家庭成员通过国际减肥手术登记处， 来自爱荷华州大学医院的明显肥胖的儿童和成人 和诊所及其家庭成员; 2）筛选突变， 通过使用来自脂肪组织的DNA，RNA， 和血浆瘦素水平和结合特性;和3）继续遗传 通过建立基因型，对爱荷华州马斯卡廷的人群进行分析， 在啮齿动物肥胖基因的同源物内或附近的多态性基因座， 分析从全基因组搜索鉴定的另外的基因座，和 将这些基因型与体型的表型测量相关联， 血浆瘦素水平 通过从这些大群体中获得样本， 我们还将建立一个DNA、RNA和血浆库，以备将来研究之用 随着技术的发展。

Obesity is a chronic disease with a high and rising prevalence, multiple physical and mental health complications, no cure, and an unknown etiology. Recent scientific work has identified multiple genetic causes of obesity in rodents, thus laying the foundation for unraveling the complex network of biologic pathways controlling body fat content. Paramount to identifying inherited factors producing human obesity is the acquisition of biologic samples from phenotypically well- characterized large populations with large numbers of nuclear families. The rapidly-advancing field of human genome analysis will provide improved technology for use in our study. Our hypothesis is that obesity is a heterogeneous disorder resulting from a combination of allelic differences in multiple genetic loci, some of which may be the human homologs of rodent obesity genes. We will continue our study entitled "The Genetic Epidemiology of Childhood Obesity" by carrying out these specific aims: 1) conduct a genome-wide search using multipoint linkage analysis and a candidate gene association study using TDT analysis by recruiting a new study population of previously-operated Bariatric Surgery patients and their family members through the International Bariatric Surgery Registry, and markedly obese children and adults from the University of Iowa Hospitals and Clinics and their family members; 2) screen for mutations in candidate genes for obesity by employing DNA, RNA from adipose tissue, and plasma leptin levels and binding properties; and 3) continue genetic analysis of the Muscatine, Iowa population by establishing genotypes at polymorphic loci within or near homologs of rodent obesity-genes, analyzing additional loci identified from a genome-wide search, and correlating these genotypes with phenotypic measures of body size and plasma leptin levels. By obtaining specimens from these large cohorts, we will also establish a bank of DNA, RNA and plasma for future study as the technology evolves.