Genetic Association in Human Asthma Populations

哮喘和慢性阻塞性肺疾病（COPD）是最常见的慢性疾病， 肺。遗传学方法可以阐明这些疾病的原因，从而提供治疗的希望。 为预防和治疗提供了新的途径。我们将进行全基因组关联 哮喘及其肺功能表型的研究（支气管扩张剂反应性和肺功能测定 肺功能（使用支气管扩张剂后FEVi和FEV/FVC比值）。我们将对317，504个HapMap SNP进行基因分型， CAMP研究中的400个哮喘儿童核心家庭。我们将确定潜在的区域 包含哮喘及其肺功能表型的遗传决定因素，使用PBAT筛查 算法，我们将正式测试这些地区使用FBAT。复制：我们将尝试复制 Specific Aim 1基因分型的SNPs与哮喘或其肺功能之间的最显著相关性 表型：对于哮喘，通过分析3，072个SNP与哮喘之间的关联， 对400例哮喘患者和400例对照者进行Sepracor/EMGB肺功能表型研究， 分析这3，072个特异性目的2b基因型SNP与肺功能之间的关联 Sepracor 400例哮喘患者的表型。哮喘易感基因的鉴定 和/或COPD：我们将对哮喘和/或COPD潜在易感基因中的1536个SNP进行基因分型 （由项目1中哮喘及其肺功能表型的全基因组关联研究确定， 项目2中COPD候选基因关联研究，以及哮喘和COPD相关QTL研究 项目3中小鼠的表型）在三项哮喘研究中：CAMP研究中的694个亲子三人组（包括 所有白色、非洲裔美国人和西班牙裔三人组），Sepracor /EMGB研究中的400例病例和400例对照， 以及哥斯达黎加的600个哮喘儿童核心家庭。我们将使用家庭为基础的病例对照 关联分析以鉴定与哮喘和/或COPD相关的基因。该研究项目将 利用新的和互补的方法（全基因组关联研究，候选基因 关联研究和小鼠遗传学研究），以寻找哮喘的主要易感基因， 确定一组影响哮喘和COPD基因。

Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic diseases of the lung. Genetic approaches may elucidate the causes of these diseases and thus offer the promise of providing new avenues for their prevention and treatment. We will perform a genome-wide association study of asthma and its lung function phenotypes (bronchodilator responsiveness and spirometric measures of lung function (post bronchodilator FEVi, and FEV^FVC ratio). Wewill genotype 317,504 HapMap SNPs in 400 nuclear families of children with asthma in the CAMP study. We will identify regions potentially containing genetic determinants of asthma and its lung function phenotypes using the PBAT screening algorithm, and we will formally test those regions using FBAT. Replication: Wewill attempt to replicate the most significant associations between SNPs genotyped in Specific Aim 1 and asthma or its lung function phenotypes: For asthma, by performing an analysis of association between 3,072 SNPs and asthma in the Sepracor/EMGB study of 400 cases of asthma and 400 controls, for lung function phenotypes, by performing an analysis of association between these 3,072 SNPs genotyped for Specific Aim 2b and lung function phenotypes among 400 cases of asthma in Sepracor. Identification of Susceptibility Genes for Asthma and/or COPD: We will genotype 1536 SNPs in potential susceptibility genes for asthma and/or COPD (identified by the genome-wide association study of asthma and its lung function phenotypes in Project 1, by candidate-gene association studies of COPD in Project 2, and by QTL studies of asthma and COPD-related phenotypes in mice in Project 3) in three asthma studies: 694 parent-child trios in the CAMP study (including all white, African-American and Hispanic trios), 400 cases and 400 controls in the Sepracor /EMGB study, and 600 nuclear families of children with asthma in Costa Rica. We will use family-based and case- control association analysis to identify genes associated with asthma and/or COPD. This research project will utilize novel and complementary approaches (genome-wide study of association, candidate-gene association studies, andgenetic studies in mice) to findmajor susceptibility genes for asthma andto identify asubset of genes that influence both asthma and COPD.