Whole Genome Analyses for Asthma in Latino Populations

拉丁裔人群哮喘的全基因组分析

• 批准号: 8230694
• 负责人: Esteban Gonzalez Burchard
• 金额: $ 72.57万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8230694
• 关键词: Admixture; African; Albuterol; Alleles; Arts; Ascaridil; Asthma; Bioinformatics; Biological Process; Bronchodilator Agents; Characteristics; Clinical; Clinical Data; Complement; Complex; DNA; Data; Disease; Disease susceptibility; Environmental Risk Factor; Epidemiology; Etiology; European; Fibrinogen; GALA; Gene Chips; Gene Frequency; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genomics; Genotype; Goals; Healthy People 2010; Hispanics; Individual; Latino; Maps; Methods; Mexican; Native Americans; Nucleic Acid Regulatory Sequences; Parents; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Prevalence; Principal Investigator; Puerto Rican; Race; Regulator Genes; Regulatory Element; Risk; Risk Factors; Sample Size; Severities; Single Nucleotide Polymorphism Map; Socioeconomic Factors; Subgroup; Testing; United States; Variant; case control; comparative genomics; gene environment interaction; genome wide association study; genome-wide; health disparity; novel; programs; racial and ethnic; response; Admixture; African; Albuterol; Alleles; Arts; Ascaridil; Asthma; Bioinformatics; Biological Process; Bronchodilator Agents; Characteristics; Clinical; Clinical Data; Complement; Complex; DNA; Data; Disease; Disease susceptibility; Environmental Risk Factor; Epidemiology; Etiology; European; Fibrinogen; GALA; Gene Chips; Gene Frequency; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genomics; Genotype; Goals; Healthy People 2010; Hispanics; Individual; Latino; Maps; Methods; Mexican; Native Americans; Nucleic Acid Regulatory Sequences; Parents; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Prevalence; Principal Investigator; Puerto Rican; Race; Regulator Genes; Regulatory Element; Risk; Risk Factors; Sample Size; Severities; Single Nucleotide Polymorphism Map; Socioeconomic Factors; Subgroup; Testing; United States; Variant; case control; comparative genomics; gene environment interaction; genome wide association study; genome-wide; health disparity; novel; programs; racial and ethnic; response

DESCRIPTION (provided by applicant): In the United States, asthma prevalence is highest in Puerto Ricans (26%) and lowest in Mexicans (10%). This is paradoxical since both groups are considered "Hispanic" or "Latino". Although there are many potential explanations for this observation, including environmental and socioeconomic factors, one potential explanation is that the genetic predisposition to asthma differs among subgroups within the Latino population. Latinos are admixed and share varying proportions of African, Native American and European ancestry. The mixed ancestry of Latinos provides unique opportunities in epidemiological and genetic studies and may be useful in untangling complex gene-gene and gene-environment interactions in disease susceptibility. This proposal will take advantage of clinical data and genomic DNA on 2,100 Puerto Rican and 1,500 Mexican asthma cases and controls collected as part of two large studies of asthma in Latinos (GALA 1 and GALA 2). The goal of this proposal is to perform genome-wide association analyses to identify genetic factors associated with asthma and related phenotypes in Puerto Ricans and Mexicans. In addition, potential interactions between these genetic factors and other genes and environmental variables will be investigated. Specifically, we will: 1) genotype Puerto Rican and Mexican asthma cases and controls using the Affymetrix state-of-art 500K GeneChip arrays, 2) perform genome-wide association analysis on 500K GeneChip data to identify SNPs associated with asthma, asthma severity and bronchodilator response. The analysis will include clinical and demographic characteristics, environmental factors and individual admixture estimates to correct for potential confounders. In addition, admixture mapping analysis will be performed to complement the genome-wide association analysis. Admixture mapping may identify novel regions that harbor racial/ethnic specific alleles for asthma and related phenotypes; and 3) fine map SNPs significantly associated with asthma and related phenotypes in genome-wide analyses (initial-hit SNPs). To our knowledge this is the first proposal to perform a genome-wide association analysis for asthma and related phenotypes in Latinos. Due to the size and scope of this project, the results of this study should substantially increase our understanding of the etiology of asthma and drug response. By gaining a better understanding of asthma risk factors in diverse populations, this proposal is consistent with the goals established by Healthy People 2010, which are to eliminate health disparities among different segments of the population.

描述（由申请人提供）：在美国，波多黎各人的哮喘患病率最高（26％），墨西哥人最低（10％）。这是自相矛盾的，因为这两个群体都被认为是“西班牙裔”或“拉丁裔”。尽管对该观察结果有许多潜在的解释，包括环境和社会经济因素，但一种潜在的解释是，在拉丁裔人群中亚组之间哮喘的遗传易感性有所不同。拉丁美洲人被混合并分享了不同比例的非洲，美洲原住民和欧洲血统。拉丁美洲人的混合血统在流行病学和遗传研究中提供了独特的机会，并且可能在疾病易感性中弄清复杂的基因基因和基因环境相互作用。该提案将利用2,100次波多黎各人的临床数据和基因组DNA和1,500个墨西哥哮喘病例，并作为拉丁美洲裔哮喘的两项大型研究（Gala 1和Gala 2）收集的一部分。该提案的目的是进行全基因组关联分析，以确定波多黎各人和墨西哥人中与哮喘和相关表型相关的遗传因素。此外，将研究这些遗传因素与其他基因与环境变量之间的潜在相互作用。具体而言，我们将：1）使用Affymetrix Arf-Art-Art 500K Genechip阵列，2）对500K Genechip数据进行全基因组的关联分析，以识别与哮喘，哮喘严重程度和Bronchodilator响应相关的SNP，使用Affymetrix Arf-Art-Art 500K Genechip Aralays使用Affymetrix Arf-Art Art-Art 500K Genechip阵列进行基因型基因型和对照。该分析将包括临床和人口统计学特征，环境因素和单个混合估计，以纠正潜在的混杂因素。此外，将进行混合图分析以补充全基因组关联分析。混合图可以确定具有哮喘和相关表型的种族/种族特定等位基因的新型区域。 3）精细的MAP SNP与全基因组分析中的哮喘和相关表型显着相关（初始击中SNP）。据我们所知，这是对拉丁美洲裔哮喘和相关表型进行全基因组关联分析的第一个建议。由于该项目的规模和范围，这项研究的结果应大大增加我们对哮喘和药物反应病因的理解。通过更好地了解不同人群中哮喘风险因素，该提案与2010年健康人建立的目标一致，这些目标是消除不同人群不同阶层之间的健康差异。