Evaluating Genes Reported to be Associated with Obesity

评估与肥胖相关的基因

• 批准号: 6858735
• 负责人: Helen N Lyon
• 金额: $ 12.77万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858735
• 关键词: body physical activity; cardiovascular disorder; child (0-11); clinical research; diabetes risk; diet; disease /disorder proneness /risk; epidemiology; gene environment interaction; gene expression; genetic screening; human data; human tissue; mass spectrometry; obesity; polymerase chain reaction; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Obesity is a public health epidemic, with no effective, feasible treatments. The recent increase in obesity, particularly in children, will bring an increase in related diseases such as diabetes and heart disease. Although the recent increase in obesity is due to changes in environmental factors such as diet and exercise, an individual's susceptibility to these environmental triggers varies with their genetic background. Knowledge of the causal genetic factors would indicate which pathways are altered in patients and would therefore guide the development effective preventive measures and treatments. No genetic variants have been proven to contribute to obesity in the general population, but recent research has provided tantalizing clues. Seventy-one common genetic variants called SNPs (single nucleotide polymorphisms) in 55 genes have been reported to be associated with obesity, but none have been replicated consistently. A recent meta-analysis of association studies suggests that many of these associations will turn out to be spurious, but also that some of these variants will represent true causal risk factors for obesity, and that large cohorts are required to make this distinction. The goal of this proposed research is to determine which of these previously reported associations represent real obesity risk factors and which are false leads. To accomplish this goal, we plan to test the 25 genes for association to obesity in multiple large, well-powered populations of lean and obese individuals (n > 4,000). To more completely characterize these candidate genes and to search for causal variants that might have led to the originally reported association, we will test not only the previously studied variants but also survey common variation throughout these genes by exploiting patterns of genetic variation called haplotypes. This approach will allow us to test the entire gene for causal variant(s) that might explain the original reported association with obesity. For any variants that we can validate as associated with obesity, we will also examine their role in obersity-related diseases (diabetes and cardiovascular disease), and explore gene-environment interactions with diet and physical activity. Finally, to set the stage for future research in early-onset obesity, we will collect a pilot cohort of children for genetic epidemiologic studies of obesity.

描述（由申请人提供）： 肥胖是一种公共卫生流行，没有有效的，可行的治疗方法。最近的肥胖症，尤其是在儿童中，肥胖症的增加将带来糖尿病和心脏病等相关疾病的增加。尽管最近肥胖的增加是由于饮食和运动等环境因素的变化所致，但个人对这些环境触发因素的敏感性随遗传背景而变化。对因果遗传因素的了解将表明患者的哪些途径发生了变化，因此将指导开发有效的预防措施和治疗。尚无遗传变异证明会导致普通人群的肥胖，但最近的研究提供了诱人的线索。据报道，55个基因中称为SNP（单核苷酸多态性）的71种常见遗传变异与肥胖有关，但没有一贯复制。最近对关联研究的荟萃分析表明，其中许多关联将被证明是虚假的，但其中一些变体将代表肥胖的真正因果风险因素，并且需要大量的同类群体来区分这种区别。这项拟议的研究的目的是确定这些先前报道的关联中的哪些代表了实际的肥胖风险因素，哪些是错误的铅。为了实现这一目标，我们计划测试25个基因与肥胖者的肥胖症相关性，这些基因是瘦和肥胖个体的多个大型，能力供电的人群（n> 4,000）。为了更彻底地表征这些候选基因并寻找可能导致最初报道关联的因果变异，我们将不仅测试先前研究的变体，而且还通过利用称为单倍型的遗传变异模式来调查整个这些基因的共同变异。这种方法将使我们能够测试整个基因的因果变异，这可能解释了原始报道的与肥胖的关联。对于我们可以与肥胖相关的任何变体，我们还将检查它们在与欧伯特相关疾病（糖尿病和心血管疾病）中的作用，并探索与饮食和体育活动的基因环境相互作用。最后，为了为未来的早期肥胖症进行研究奠定阶段，我们将收集一群儿童的试点，以进行肥胖的遗传流行病学研究。