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

项目总结/摘要 哮喘的负担在少数民族儿童中特别高，特别是非洲儿童。 血统.非裔美国人（AA）儿童住院的可能性是其他儿童的四倍， 死于哮喘的可能性更大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，这些因素相互作用来解释一个人的哮喘风险的程度 哮喘的风险在很大程度上仍然未知。我们的长期目标是制定一项研究计划， 深入了解哮喘的遗传和非遗传原因之间的复杂相互作用， AA儿童，并建立这些信息的效用，以减少和预测儿童哮喘的风险。的 本研究的目的是探讨遗传祖先和环境暴露之间的相互作用 使用DNA库的特征队列研究AA儿童中哮喘风险的危险因素 样本、环境暴露和临床数据以及祖先信息标记。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， 非洲和欧洲血统可能是目前非洲哮喘风险差异的部分原因。 美国混血血统。此外，祖先和环境暴露可能共同影响 哮喘的变化和发展。提出了两个具体目标来检验我们的假设，并实现我们的目标。 提出的计划：目的1）使用祖先确定AA哮喘儿童的本地和全球遗传祖先 信息标记（AIM）;和目标2）确定当地祖先和环境之间的相互作用 暴露风险因素。这项拟议的研究非常重要（它解决了一个重大的公共卫生问题， 少数民族儿童哮喘的高负担）和高度创新（它剖析了遗传和非遗传因素， 使用祖先作图的哮喘差异的遗传原因）。最终，这项研究可能会提供 以及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。 成功申请R 03将为申请可资助的R 01赠款提供关键知识和数据 儿童哮喘的种族差异。因此，我们认为，这项试点研究沿着 未来的研究将揭示遗传因素和选择的环境因素是否 暴露因素及其相互作用可以影响哮喘风险和预测，从而减轻负担 哮喘对患者及其家属的影响，并改善他们的生活质量。 1