On the Genetic Determinants of Asthma and Obesity

描述(申请人提供)：在过去的二十年里，肥胖和哮喘在美国的流行程度已经达到流行病的程度：超过三分之一的美国人口符合肥胖的临床定义，11.2%的人将在他们的一生中被诊断为哮喘。这些情况造成了过高的公共卫生负担。它们每年的成本加起来超过1000亿美元。由于这些疾病如此普遍，任何治疗或预防方面的改进都将大大降低医疗成本，减轻公共卫生负担。尽管这些疾病受到环境因素的影响，但研究表明，肥胖和哮喘是具有遗传病因的复杂疾病，遗传率估计分别为75%和81%。但是，哮喘和肥胖的遗传病因只被独立研究过，尽管来自20多项流行病学研究的证据表明，哮喘与先前存在的肥胖呈正相关，这种关系可能部分归因于共同的基因决定因素。识别同时影响哮喘和肥胖症的基因变异有望在两个方面改善治疗和预防，从而更有效地减轻公共卫生负担。我们的中心假设是哮喘和肥胖症有共同的基因决定因素。在这项提案中，我们试图确定这些常见的遗传变异。使用全基因组关联研究(GWAS)数据，我们将使用儿童哮喘管理计划(CAMP)研究的数据来确定遗传与哮喘和肥胖症的关联，该研究由422个父母-子女三人组组成。然后，我们将使用两阶段方法在三个独立和不同种族的队列中复制排名前200的协会。首先，我们将对哥斯达黎加611个亲子三人组中的200个单核苷酸多态(SNPs)进行基因分型和分析。然后，我们将确定具有最强关联性的50个SNP。在第二阶段，我们将在两个队列中对这50个SNP进行分型和分析：1)深红高加索人：2000名哮喘患者和2000名对照；以及2)深红非裔美国人：1,000名哮喘患者和1000名对照。一旦我们确定了一组与哮喘和肥胖症一致相关的SNPs，我们将确定这些观察到的关联背后的因果关系。

DESCRIPTION (provided by applicant): The prevalence of obesity and asthma over the last two decades has reached epidemic proportions in the United States: more than a third of the U.S. population meets the clinical definition of obesity, and 11.2% will be diagnosed with asthma during their lifetimes. These conditions create an exorbitant public health burden. Together, their costs exceed $100 billion each year. Because these diseases are so prevalent, any improvement in treatment or prevention will substantially reduce healthcare costs and ease the public health burden. Although these diseases are influenced by environmental factors, research suggests that obesity and asthma are complex disorders that have genetic etiologies, with heritability estimates of 75% and 81%, respectively. But the genetic etiologies for asthma and obesity have only been studied independently, despite evidence from more than 20 epidemiological studies that suggests asthma is positively associated with preexisting obesity and that this relationship may be due in part to shared genetic determinants. Identifying genetic variants that influence both asthma and obesity promises to improve treatment and prevention on two fronts, thereby more effectively relieving the burden on public health. Our central hypothesis is that there are common genetic determinants for asthma and obesity. In this proposal we seek to identify these common genetic variants. Using genome-wide association study (GWAS) data, we will identify genetic associations with asthma and obesity using data from the Childhood Asthma Management Program (CAMP) study which consists of 422 parent-offspring trios. We will then replicate the top 200 associations in three Independent and ethnically diverse cohorts using a two phase approach. First we will genotype and analyze 200 single nucleotide polymorphisms (SNPs) In a Costa Rican cohort of 611 parent-offspring trios. We will then identify the 50 SNPs with the strongest associations. In the second phase we will genotype and analyze these 50 SNPs in two cohorts: 1) Crimson Caucasian: a sample of 2,000 asthmatic cases and 2,000 controls; and 2) Crimson African American: a sample of 1,000 asthmatic cases and 1,000 controls. Once we identify a set of SNPs that are consistently associated with asthma and obesity, we will determine the causal pathway behind the observed associations.