The Genetic Epidemiology of Asthma in Costa Rica

4 R37 HL066289-10-功绩扩展首席调查员/项目总监(最后、第一、中间)：Weiss，Scott T. 项目SuIVIMARY(请参阅说明)： 哮喘仍然是美国和全世界的一个主要公共卫生问题，影响着3亿人 美国人的医疗保健费用为200亿美元/年。哮喘可能是一种复杂的疾病 受遗传和环境因素的影响。哮喘遗传流行病学已经取得了重大进展 通过候选基因研究确定了43个基因，通过连锁和精细定位确定了6个基因 3个基因通过全基因组关联研究(GWAS)。 尽管哮喘是美国某些拉美裔群体发病率的重要原因(例如， 波多黎各人)和拉美裔美国人(例如哥斯达黎加人)，包括的基因研究相对较少 西班牙裔个人。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，在西班牙裔中哮喘的患病率和严重程度存在显著差异 亚群，使得拉美裔哮喘的基因研究特别具有挑战性。为了减少这一点 异质性，我们一直在研究相对同质的西班牙裔哮喘的遗传学 年哥斯达黎加中央山谷哮喘高发人群(青少年约24%) 过去的8年里。 为了这次更新，我们将我们的哥斯达黎加人与营地三人组结合起来，试图 找出儿童哮喘的所有基因。我们将继续为增进我们的理解做出贡献 通过使用新的方法寻找复制的哮喘基因来研究哮喘遗传学。此外，多套 这项资助申请的研究提供了独特的机会来识别基因 哮喘的决定因素是拉美裔人群特有的，同时也是普遍存在的 与西班牙裔和高加索人群相关的遗传决定因素将是 被发现了。为了确定这些变种，我们将对可用的GWA进行三种不同的联合分析： 将对哥斯达黎加和坎普进行联合分析，然后对哥斯达黎加进行计算机元分析。 来自EVE财团的哥斯达黎加和墨西哥三人组，最后，对哥斯达黎加、坎普、 还有伊芙。 我们相信，通过进行我们提议的全基因组关联研究，我们将拥有最多 强大而全面的方法来识别哮喘易感基因，以及我们的 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 在大路疾病遗传学中创建一个生物信息集成计划。 相关性(请参阅说明)： 到目前为止，只有一项关于哮喘和/或其中间体的全基因组相关性研究。 西班牙裔(墨西哥)人群的表型。我们的研究解决了一个研究不足的问题： 受哮喘影响不成比例的西班牙裔亚群中的哮喘遗传学：一般情况下西班牙裔和 尤其是哥斯达黎加人。这一建议应该导致在中国发现哮喘易感基因 一般情况下，特别是在拉美裔中。

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.