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

基本信息

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
项目类别：
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

项目摘要

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

项目概要/摘要少数民族儿童，尤其是非洲儿童的哮喘负担异常高非裔美国人 (AA) 儿童住院的可能性是其他人的四倍，是其他人的七倍。最近的研究表明，患有哮喘的人比患有哮喘的人更有可能因遗传和环境暴露而死亡。导致哮喘风险的因素；然而，这些因素相互作用的程度可以解释一个人的哮喘风险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，以实现以下目标：深入了解哮喘的遗传和非遗传原因之间复杂的相互作用 AA 儿童，并确立此信息在降低和预测儿童哮喘风险方面的效用。本研究的目的是调查遗传血统与环境暴露之间的相互作用使用 DNA 库进行充分表征的队列研究导致 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祖先信息标记。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此外，血统和环境暴露可能共同影响美国人的混血血统。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) 使用血统确定 AA 哮喘儿童的局部和整体遗传血统目标 2) 确定当地血统与环境之间的相互作用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）最终，这项研究可能会提供联系。深入了解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因此，我们认为这项试点研究与儿童哮喘的种族差异有关。未来的研究将揭示有关遗传因素和选定的环境是否暴露因素及其相互作用可以影响哮喘风险和预测，从而减轻负担减少哮喘对患者及其家人的影响，提高他们的生活质量。 1