The Genetic Epidemiology of Asthma in Costa Rica

4 R37 HL 066289 -10 - MERIT扩展期主要研究者/项目负责人（最后、第一、中间）：韦斯，Scott T. 项目随附资料（见说明）： 哮喘仍然是美国和全世界影响3亿人的主要公共卫生问题 美国每年的医疗费用超过200亿美元。哮喘是一种复杂的疾病， 受遗传和环境因素的影响。哮喘的遗传流行病学已经使 通过候选基因研究确定了超过43个基因，通过连锁和精细定位确定了6个基因， 通过全基因组关联研究（GWAS）对3个基因进行了分析。 虽然哮喘是美国某些西班牙裔群体发病的重要原因（例如， 波多黎各人）和西班牙裔美国人（例如，哥斯达黎加人），相对较少的遗传研究包括 西班牙裔人。大多数--但不是全部--西班牙裔有不同比例的欧洲人，美洲印第安人， 和非洲血统，并且西班牙裔美国人的哮喘患病率和严重程度存在显著差异 亚群，使得西班牙裔哮喘的遗传研究特别具有挑战性。减少这种 异质性，我们一直在研究哮喘的遗传学在一个相对同质的西班牙裔 哥斯达黎加中央谷哮喘高发人群（青少年约24%）， 过去的八年。 为了这次更新，我们将哥斯达黎加人口与CAMP三人组结合起来， 找出儿童哮喘的所有基因。我们将继续为增进我们的理解作出贡献 通过使用新的方法来寻找复制的哮喘基因。此外，多套 研究可用于此拨款申请，以提供独特的机会，以确定遗传 西班牙裔人群特有的哮喘决定因素，同时， 与西班牙裔人群和高加索人群相关的遗传决定因素将是 发现了为了识别这些变体，我们将对可用的GWAS进行三种不同的联合分析： 将对哥斯达黎加和CAMP进行联合分析，然后对哥斯达黎加进行计算机Meta分析 哥斯达黎加和墨西哥三重奏从EVE财团，最后，一个整体分析哥斯达黎加，CAMP， 和夏娃。 我们相信，通过进行我们提出的全基因组关联研究，我们将拥有最多的 一种强大而全面的方法来鉴定哮喘易感基因， 生物信息学工具将使我们能够充分利用从实验中获得的信息， 创建一个生物信息学整合的安韦病遗传学项目。 相关性（参见说明）： 到目前为止，只有一项关于哮喘和/或其中间型的全基因组关联研究， 西班牙裔（墨西哥）人群中的表型。我们的研究解决了一个研究不足的问题： 西班牙裔亚群中哮喘的遗传学不成比例地受到哮喘的影响：西班牙裔总体和 尤其是哥斯达黎加人。这一建议将导致哮喘易感基因的鉴定， 一般来说，尤其是西班牙裔。

4 R37 HL066289-10 - MERIT Extension Principal Investigator/Program Director (Last, First, Middle): WEISS, Scott T. PROJECT SUIVIMARY (See instructions): Asthma remains a major public health problem in the United States and worldwide affecting 300 million people in the US with health care costs of >20 billion dollars/year. Asthma Is a complex disease, likely influenced by genetic and environmental factors. Asthma genetic epidemiology has made significant progress identifying over 43 genes via candidate gene studies, 6 genes via linkage and fine mapping and 3 genes via genome-wide association studies (GWAS). Although asthma is a significant cause of morbidity among certain Hispanic groups in the US (e.g., Puerto Ricans) and Hispanic America (e.g., Costa Ricans), relatively few genetic studies have included Hispanic individuals. Most - but not all - Hispanics have variable proportions of European, Amerindian, and African ancestry, and there is marked variation in asthma prevalence and severity within Hispanic sub-populations, making genetic studies of asthma in Hispanics particularly challenging. To reduce this heterogeneity, we have been studying the genetics of asthma in a relatively homogeneous Hispanic population with high prevalence of asthma (~24% in adolescents) in the Central Valley of Costa Rica for the past 8 years. For this renewal, we have combined our Costa Rican population with the CAMP trios to attempt to identify all the genes for childhood asthma. We will continue to contribute to advancing our understanding of asthma genetics by using novel methods to find replicated asthma genes. In addition, multiple sets of studies are available for this grant application to provide the unique opportunity to identify genetic determinants of asthma that are specific to Hispanic populations, while, at the same time, universal genetic determinants that are relevant for Hispanic populations and Caucasian populations will be discovered. To identify these variants we will perform three different joint-analysis of the available GWAS: a joint analysis of Costa Rica and CAMP will be performed, followed by an in silico meta analysis of Costa Rica and Mexican trios from the EVE consortium and, finally, an overall analysis of Costa Rica, CAMP, and EVE. We believe that by conducting our proposed genome-wide association study, we will have the most powerful and comprehensive approach to identification of asthma-susceptibility genes, and our bioinformatics tools will allow us to take full advantage of information deriving from our experiments to create a bioinformatically-integrated program in ainway disease genetics. RELEVANCE (See instructions): To date, there has been only one genome-wide association study of asthma and/or its intermediate phenotypes in a Hispanic (Mexican) population. Our study addresses an insufficiently studied problem: the genetics of asthma in Hispanic subgroups disproportionately affected by asthma: Hispanics in general and Costa Ricans in particular. This proposal should lead to the identification of asthma-susceptibility genes in general, and among Hispanics in particular.