Whole Genome Analyses for Asthma in Latino Populations

拉丁裔人群哮喘的全基因组分析

基本信息

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
项目类别：
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

项目摘要

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%），墨西哥人的患病率最低（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”。尽管这一观察结果有许多可能的解释，包括环境和社会经济因素，但一个可能的解释是拉丁裔人群中不同亚群体的哮喘遗传易感性不同。拉丁美洲人是混血儿，具有不同比例的非洲、美洲原住民和欧洲血统。拉丁裔的混合血统为流行病学和遗传学研究提供了独特的机会，并且可能有助于解开疾病易感性中复杂的基因-基因和基因-环境相互作用。该提案将利用作为两项大型拉丁裔哮喘研究（GALA 1 和 GALA 2）的一部分收集的 2,100 名波多黎各和 1,500 名墨西哥哮喘病例和对照的临床数据和基因组 DNA。该提案的目标是进行全基因组关联分析，以确定与波多黎各人和墨西哥人的哮喘及相关表型相关的遗传因素。此外，还将研究这些遗传因素与其他基因和环境变量之间的潜在相互作用。具体来说，我们将：1) 使用 Affymetrix 最先进的 500K GeneChip 阵列对波多黎各和墨西哥哮喘病例和对照进行基因分型，2) 对 500K GeneChip 数据进行全基因组关联分析，以确定与哮喘、哮喘严重程度和哮喘相关的 SNP。支气管扩张剂反应。该分析将包括临床和人口特征、环境因素和个体混合估计，以纠正潜在的混杂因素。此外，还将进行混合作图分析以补充全基因组关联分析。混合图谱可以识别含有哮喘和相关表型的种族/民族特异性等位基因的新区域； 3) 全基因组分析中与哮喘和相关表型显着相关的精细图谱 SNP（初始命中 SNP）。据我们所知，这是第一个针对拉丁美洲人的哮喘和相关表型进行全基因组关联分析的提案。由于该项目的规模和范围，这项研究的结果应该会大大增加我们对哮喘病因和药物反应的理解。通过更好地了解不同人群中的哮喘危险因素，该提案与《2010年健康人民》制定的目标是一致的，即消除不同人群之间的健康差异。