GENETIC EPIDEMIOLOGY OF CHILDHOOD OBESITY

肥胖是一种慢性病，患病率很高，而且还在不断上升， 身心健康方面的并发症，无法治愈，且未知 病因学。最近的科学研究发现了多种遗传原因。 对啮齿类动物肥胖的研究，从而为揭开 控制身体脂肪含量的生物通路的复杂网络。 识别导致人类肥胖的遗传因素最重要的是 从表型井中获取生物样本- 以拥有大量核心家庭的庞大人口为特征。 快速发展的人类基因组分析领域将提供 改进了我们研究中使用的技术。我们的假设是 肥胖症是一种异质性疾病，由 多个遗传座位的等位基因差异，其中一些可能是 啮齿动物肥胖基因的人类同源物。 我们将继续我们的研究，题为《人类遗传流行病学》 儿童肥胖“通过实现这些具体目标：1)开展 使用多点连锁分析的全基因组搜索和候选 TDT分析在基因关联研究中的应用 曾接受过减肥手术的患者群体及其影响因素分析 家庭成员通过国际减肥外科注册中心，以及 来自爱荷华大学医院的明显肥胖的儿童和成年人 和诊所及其家庭成员；2)筛查 通过利用来自脂肪组织的DNA、RNA， 和血浆瘦素水平和结合特性；以及3)继续遗传 爱荷华州马斯卡廷人群的基因分型分析 啮齿动物肥胖基因同源基因内或附近的多态基因座， 分析从全基因组搜索中识别的其他基因座，以及 将这些基因型别与体型和体型指标相关联 血浆瘦素水平。通过从这些大型队列中获取样本， 我们还将建立DNA、RNA和血浆库，以供将来研究 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.