Ancestry-Environmental Exposure Interactions and Asthma Risk in Admixed Population

混合人群中祖先-环境暴露相互作用和哮喘风险

• 批准号: 9170155
• 负责人: Tesfaye B. Mersha
• 金额: $ 7.8万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9170155
• 关键词: Address; Admixture; Affect; African; African American; Age; Alleles; Allergens; Applications Grants; Asthma; Biological; Caring; Child; Childhood; Childhood Asthma; Chromosomes; Clinic; Clinical Data; Complex; Custom; DNA Library; Data; Development; Environment; Environmental Exposure; European; Exhibits; Exposure to; Family; Funding; Future; Gene Frequency; Genetic; Genetic Predisposition to Disease; Genome; Genomic Segment; Genotype; Goals; Grant; Individual; Intervention; K-Series Research Career Programs; Lead; Link; Linkage Disequilibrium; Maps; Measures; Methods; Molds; National Heart, Lung, and Blood Institute; Pathway interactions; Patient Self-Report; Patients; Persons; Phenotype; Pilot Projects; Population; Principal Investigator; Public Health; Quality of life; Research; Resolution; Resources; Risk; Risk Factors; Role; Sampling; Smoke; Socioeconomic Status; Subgroup; Testing; Time; Tobacco smoke; United States; United States National Institutes of Health; Variant; Work; abstracting; asthmatic; base; cohort; data to knowledge; design; gene environment interaction; genetic variant; genome wide association study; genome-wide; high risk; improved; innovation; insight; minority children; non-genetic; novel; programs; racial disparity; repository; risk variant; sex; study population; success; tool; trafficking

Project Summary/Abstract The burden of asthma is disproportionately high among minority children, in particular children of African descent. African American (AA) children are four times more likely to be hospitalized and seven times more likely to die from asthma than non-AAs. Recent studies have identified genetic and environmental exposure factors that contribute to asthma risk; however, the extent to which these factors interact to explain a person’s risk to asthma remains largely unknown. Our long-term goal is to develop a program of study that would lead to an in-depth understanding of the complex interplay between genetic and non-genetic causes of asthma among AA children, and establish the utility of this information to reduce and predict asthma risk in children. The objective of this study is to investigate the interactions between genetic ancestry and environmental exposure risk factors contributing to asthma risk in AA children using a well characterized cohort with banked DNA samples, environmental exposure and clinical data as well as ancestry informative markers. We hypothesize that genetic variants with large allele frequency differences and variation in environmental exposures between African and European ancestry may be partly responsible for the current difference in asthma risk in African American admixed ancestry. Moreover, ancestry and environmental exposure may jointly influence the variation and development of asthma. Two Specific Aims are proposed to test our hypothesis and achieve our proposed plan: Aim 1) Determine local and global genetic ancestry in AA asthmatic children using ancestry informative markers (AIMs); and Aim 2) Identify interactions between local ancestry and environmental exposure risk factors. The proposed study is highly significant (it addresses a major public health issue given the high burden of asthma among minority children) and highly innovative (it dissects the genetic and non- genetic causes of asthma disparities using ancestry mapping). Ultimately, this research may provide the link and insight between asthma and genetic and non-genetic factors and has potential avenues for intervention. Success in this R03 application will provide key knowledge and data to apply for fundable R01 grant application related to racial disparities in childhood asthma. We therefore believe that this pilot study along with future studies will uncover fundamental information about whether genetic factors and selected environmental exposure factors as well as their interactions can affect asthma risk and prediction, thereby reducing the burden of asthma on patients and their families and improving their quality of life. 1

项目摘要/摘要 在少数民族儿童中，特别是非洲儿童，哮喘的灼伤量不成比例地高。 下降。非裔美国人（AA）儿童住院的可能性是四倍 可能会因哮喘而死。最近的研究已经确定了遗传和环境暴露 导致哮喘风险的因素；但是，这些因素在多大程度上解释一个人的 哮喘的风险在很大程度上是未知的。我们的长期目标是制定一项研究计划，这将导致 深入了解遗传和非遗传原因哮喘的复杂相互作用 AA儿童，并建立此信息的实用性，以减少和预测儿童的哮喘风险。 这项研究的目的是研究遗传血统与环境暴露之间的相互作用 使用良好特征的与银行DNA的良好表征的同类群体导致AA儿童哮喘风险的风险因素 样本，环境暴露和临床数据以及祖先的信息标记。我们假设 具有较大等位基因频率差异的遗传变异以及环境暴露之间的变化 非洲和欧洲血统可能是对非洲哮喘风险当前差异的一部分负责 美国的祖先。此外，祖先和环境暴露可能会共同影响 哮喘的变异和发展。提出了两个具体目标来检验我们的假设并实现我们的假设 拟议计划：目标1）确定AA哮喘儿童使用祖先的局部和全球遗传血统 信息标记（AIMS）；目标2）确定当地血统与环境之间的互动 暴露风险因素。拟议的研究非常重要（它解决了给定的一个重大公共卫生问题 少数族裔儿童哮喘的高燃烧）和高度创新性（它剖析了遗传和非 - 使用祖先映射的哮喘分布的遗传原因）。最终，这项研究可能会提供链接 以及哮喘与遗传和非遗传因素之间的见识，并具有潜在的干预途径。 此R03应用程序的成功将提供关键知识和数据，以申请可资金的R01赠款 与儿童哮喘中种族分布有关的应用。因此，我们认为这项试验研究以及 未来的研究将发现有关遗传因素和选定环境的基本信息 暴露因素及其相互作用会影响哮喘的风险和预测，从而减轻负担 患者及其家人的哮喘并改善了他们的生活质量。 1