On the Genetic Determinants of Asthma and Obesity

描述（由申请人提供）：在过去的二十年中，肥胖和哮喘的患病率在美国达到了流行病的程度：超过三分之一的美国人口符合肥胖的临床定义，11.2%的人将在其一生中被诊断患有哮喘。这些情况造成了沉重的公共卫生负担。它们每年的总成本超过1000亿美元。由于这些疾病非常普遍，治疗或预防方面的任何改进都将大大降低医疗保健费用，减轻公共卫生负担。虽然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遗传决定因素。确定影响哮喘和肥胖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有共同的遗传决定因素。在本提案中，我们试图确定这些常见的遗传变异。利用全基因组关联研究（GWAS）数据，我们将利用儿童哮喘管理计划（CAMP）研究的数据确定哮喘和肥胖的遗传关联，该研究由422对父母-后代三人组组成。然后，我们将采用两阶段方法在三个独立且种族多样化的队列中复制前200个协会。首先，我们将对哥斯达黎加611个父母-后代三胞胎的200个单核苷酸多态性（snp）进行基因型分析。然后，我们将确定50个snp与最强的关联。在第二阶段，我们将在两个队列中对这50个snp进行基因分型和分析：1)深红色高加索人：2000例哮喘病例和2000例对照；2)深红非洲裔美国人：1000例哮喘病例和1000例对照。一旦我们确定了一组与哮喘和肥胖一致相关的snp，我们将确定观察到的关联背后的因果途径。

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.