Ancestry-Environmental Exposure Interactions and Asthma Risk in Admixed Population

项目摘要/摘要 少数族裔儿童，特别是非洲儿童，哮喘负担过重。 下降。非裔美国人(AA)儿童住院的可能性是前者的4倍，后者的7倍 比非AAA患者更有可能死于哮喘。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；然而，这些因素相互作用解释一个人的 患哮喘的风险在很大程度上仍是未知的。我们的长期目标是制定一个学习计划，这将导致 深入了解哮喘的遗传和非遗传病因之间的复杂相互作用 AA儿童，并建立这一信息的效用，以降低和预测儿童哮喘的风险。这个 这项研究的目的是调查遗传祖先和环境暴露之间的相互作用。 使用具有良好特征的DNA库队列研究AA儿童哮喘风险的危险因素 样本、环境暴露和临床数据以及血统信息标记。我们假设 具有较大等位基因频率差异和环境暴露差异的遗传变异 非洲人和欧洲人的血统可能是目前非洲人哮喘风险差异的部分原因 美国混血血统。此外，血统和环境暴露可能会共同影响 哮喘的变异和发展。提出了两个具体的目标来检验我们的假设并实现我们的 建议计划：目的1)利用血统确定再生障碍性哮喘儿童的本地和全球遗传血统 信息性标记(AIMS)；和AIMS 2)确定当地血统和环境之间的相互作用 暴露风险因素。拟议的研究具有非常重要的意义(它解决了一个重大的公共卫生问题 少数族裔儿童的高哮喘负担)和高度创新(它剖析了遗传性和非遗传性 使用谱系图谱分析哮喘差异的遗传原因)。最终，这项研究可能会提供联系 并洞察哮喘与遗传和非遗传因素之间的关系，并具有潜在的干预途径。 R03申请的成功将为申请可资助的R01拨款提供关键知识和数据 与儿童哮喘的种族差异有关的应用。因此，我们认为，这项试点研究以及 未来的研究将揭示关于遗传因素和选定的环境 暴露因素及其相互作用可影响哮喘风险和预测，从而减轻负担 哮喘对患者及其家人的影响，并改善他们的生活质量。 1

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