New Approaches for Empowering Studies of Asthma in Populations of African Descent

非洲人后裔哮喘研究的新方法

• 批准号: 8527333
• 负责人: Kathleen C Barnes
• 金额: $ 5.73万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-28 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8527333
• 关键词: Accounting; Admixture; Affect; African; African American; African Caribbean; Americas; Area; Asthma; Baltimore; Barbados; Biomedical Research; Characteristics; Child; Clinical; Collaborations; Communities; Complement; Complex; Copy Number Polymorphism; Custom; DNA; Data; Data Analyses; Data Set; Databases; Disease; Disease Progression; Disease susceptibility; District of Columbia; Environmental Exposure; Epidemic; Ethnic group; European; Family member; Genes; Genetic; Genetic Polymorphism; Genome; Genome Scan; Genotype; Goals; Grant; IgE; Individual; Institution; International; Lead; Linkage Disequilibrium; Maps; Meta-Analysis; Minority Groups; Molecular Genetics; National Heart, Lung, and Blood Institute; Population; Population Genetics; Population Heterogeneity; Predisposition; Public Health; Research Personnel; Risk; SNP genotyping; Sample Size; Sampling; Stratification; Susceptibility Gene; Symptoms; Technology; Testing; Underrepresented Minority; Variant; asthmatic patient; base; case control; data mining; density; empowered; follow-up; forging; gene discovery; genetic association; genetic epidemiology; genetic variant; genome wide association study; genome-wide; markov model; metropolitan; novel; novel strategies; outcome forecast; sample collection; trait

DESCRIPTION (provided by applicant): Asthma is a complex disease where the interplay between genetic factors and environmental exposures has significant influence on susceptibility and disease prognosis. Asthmatics of African descent tend to have more severe asthma and more severe clinical symptoms than individuals of European ancestry, but relatively few studies have focused on this underrepresented minority group. Genome-wide association studies (GWAS) have revolutionized gene discovery for multiple complex traits, but implementation of the next step in gene discovery following GWAS of asthma among populations of African descent requires considerations unique to this ethnic group, including adequate sample sizes, population stratification due to admixture, and perhaps most importantly, an approach that recognizes that the current coverage of common variation both in the public database and particularly on commercially available SNP chips is inadequate to detect true genetic association among African admixed populations. In our own GWAS on 1,000 African American asthma cases and controls from Baltimore-Washington, D.C. and 1,000 African Caribbean asthmatics and their family members from Barbados, we have identified suggestive associations for which replication is not observed in populations of European descent, supporting the hypothesis that populations of African descent may carry unique susceptibility loci. We have forged a collaboration of investigators representing 12,000 DNA samples from well-characterized African American and African Caribbean asthmatic patients and healthy controls and/or family members from which six studies (5,000 samples) have GWAS data available for meta-analysis and seven populations (>7,000 samples) are available for replication. In this application, we propose four specific aims: (i) we will leverage discoveries in the 1,000 Genomes Project and data-mine for novel SNPs in African and African admixed populations develop a custom, African-ancestry gene-centric 200K SNP genotyping array ('African Power Chip') to complement current, commercially available GWAS chips, for which common and rare variants are not adequately tagged by the existing SNPs, and thereby facilitate GWAS studies on populations of African descent; (ii) we will perform genotyping on DNA samples with existing GWAS data among the 'Consortium on Asthma among African-ancestry Populations in the Americas' (CAAPA) and test for associations with asthma, followed by; (iii) in-depth analyses including imputation-based association mapping of asthma loci, copy number variant (CNV) analyses, and admixture mapping; and (iv) replicate the most significant associations in independent samples available through CAAPA. Results from these studies will lead to substantial advancements in the technology available for identifying genes relevant to disease for what is one of the most underrepresented minorities in biomedical research, African ancestry populations, and will generate deliverables to the scientific community at large, both as an invaluable database and as a validated SNP chip.

描述（由申请人提供）：哮喘是一种复杂的疾病，其中遗传因素与环境暴露之间的相互作用对易感性和疾病预后具有重大影响。与欧洲血统的人相比，非洲血统的哮喘患者往往具有更严重的哮喘和更严重的临床症状，但相对较少的研究集中在这个代表性不足的少数群体上。全基因组的关联研究（GWAS）已彻底改变了基因发现的多种复杂特征，但是在非洲血统人群中，基因发现的下一步的实施需要考虑到这个族裔群体所特有的考虑因素，包括适当的样本大小，包括大小的人口分层，尤其是对当前的普通范围，既可以识别的，又是公开范围的，这两种范围都在公共范围内，以及在公共方面的范围，并涉及普通的范围，这些杂物是普通的范围。筹码不足以检测非洲混合群体之间的真正遗传关联。在我们对1000名非裔美国人哮喘病例和巴尔的摩 - 华盛顿特区和1000名非洲加勒比海哮喘患者及其来自巴巴多斯的家庭成员的GWA中，我们确定了在欧洲血统中没有观察到的复制性的暗示性关联，支持了非洲人的群体，该假设具有独特的untiment sustipitive sustipity sustipity sustigence sustigience sustigience sustigience sustibialie sustibiali sustigience。我们已经建立了一个合作的调查人员，代表了良好的非裔美国人和非洲加勒比海哮喘患者和健康对照组和/或家庭成员的12,000个DNA样品，其中有六项研究（5,000个样本）可用于荟萃分析和七个人群（> 7,000个样本（> 7,000个样本），可用于复制。在此应用程序中，我们提出了四个具体目的：（i）我们将在1000个基因组项目和数据中的发现中的发现，用于非洲和非洲人口中的新型SNP，发展了一种习俗，非洲基因基因200k SNP SNP基因分型阵列（非洲力量chip'的标签，并不适用，这是不可接受的，并且在gwas coplect and comporty snpers，这是常见的，这是常见的，这是常见的，这是常见的，这是一种常见的变化，这种变化是，这种变化是，这种变化是，这种变化是，这种变化是，这种变化是，这种变化是，这是不可思议的。从而促进GWAS对非洲血统人群的研究； （ii）我们将对“美洲非洲官员人群中的哮喘联盟”（CAAPA）和与哮喘的关联进行测试，对DNA样本进行基因分型。 （iii）深入分析，包括哮喘基因座的基于插补的关联映射，拷贝数变体（CNV）分析和混合映射； （iv）复制通过CAAPA获得的独立样本中最重要的关联。这些研究的结果将导致可用于识别与疾病相关的基因的实质性进步，这是生物医学研究中最多代表的少数群体之一，非洲血统人群，并将为整个科学界（作为一个无价的数据库和有效的SNP CHIP）为大型科学界产生可交付成果。