Unraveling ancestry and environmental exposure interactions in childhood asthma

揭开儿童哮喘的祖先和环境暴露的相互作用

基本信息

批准号：
9246597
负责人：
Tesfaye B. Mersha
金额：
$ 67.66万
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：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9246597
关键词：
Address Admixture Affect African African American Age Architecture Asthma Caring Child Childhood Childhood Asthma Clinic Clinical Data Complex Computerized Medical Record DNA Data Development Disease Environmental Exposure Environmental Risk Factor Etiology European Exhibits Exposure to Gene Frequency Genetic Genome Genomic Segment Genotype Goals Haplotypes Individual K-Series Research Career Programs Lead Medical center Molds Morbidity - disease rate Patient Self-Report Pattern Pediatric Hospitals Persons Phenotype Population Positioning Attribute Predisposition Principal Investigator Probability Protocols documentation Public Health Race Research Research Design Risk Risk Factors Running Sample Size Sampling Socioeconomic Status Subgroup Testing Time Translational Research United States Variant admixture mapping asthmatic base biobank cigarette smoking cohort conditioning design epidemiologic data gene environment interaction genome wide association study genome-wide improved innovation insight minority children novel predictive modeling programs public health intervention public health relevance repository risk variant sex study population success

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposed research is to determine to what extent asthma risk in African American (AA) subjects is modified by environmental exposure risk factors. Recent studies have identified genetic and environmental exposure factors that contribute to asthma risk; however, the extent to which these factors 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 ancestry and environmental causes of asthma among AA children, and establish the utility of this information to predict and reduce asthma risk in AA children. Despite advances in asthma care, AAs are four times more likely to be hospitalized and seven times more likely to die from asthma than non-AAs. AAs have a mixed parental genome contribution with varying proportion of ancestry from African and European descents. We plan to search for specific genomic regions of unusually high African or European ancestry to identify chromosomal segments that are likely to interact with environmental exposure asthma risk factors. We hypothesize that ancestry and environmental exposure risk factors are critical in asthma risk. Three Specific Aims are proposed to test our hypothesis and achieve our proposed plan: Aim 1) Determine the genetic ancestry and conduct admixture mapping of AA asthmatic children using a multi-ethnic genotyping array; Aim 2) Identify interactions between local ancestry and environmental exposure risk factors in modifying asthma risk; and Aim 3) Replicate the most promising ancestry-specific and A:E interacting 6000 SNPs and develop a genetic ancestry risk score (GARS) to potentially explain a significant portion of asthma risk. To complete these aims we will analyze genetic, environmental exposure factors, clinical and epidemiologic data from the Cincinnati Children's Hospital Medical Center pediatric repository cohorts and Cincinnati BioBank. This research will improve our understanding of the interplay between ancestry and environmental exposure factors (traffic, cigarette smoke, mold) that modify asthma risk. Using a unique ancestry-based study design, we are particularly well positioned to develop a roadmap to unravel the relative contributions of genetic and environmental exposure variances and uncover the etiology of asthma in minority children. Predicting the development or progression of asthma is one of the ultimate aims of our research. 1

描述（由申请人提供）：这项拟议研究的目标是确定环境暴露风险因素在多大程度上改变非裔美国人（AA）受试者的哮喘风险。最近的研究已经确定了导致哮喘风险的遗传环境暴露因素。然而，这些因素在多大程度上解释了一个人患哮喘的风险仍然很大程度上未知，我们的长期目标是制定一项研究计划，以深入了解遗传血统和环境原因之间的复杂相互作用。 AA 中的哮喘尽管哮喘护理取得了进步，但 AA 儿童住院的可能性是非 AA 儿童的四倍，死于哮喘的可能性是非 AA 儿童的七倍。具有不同比例的非洲和欧洲血统的混合父母基因组贡献我们计划寻找异常高的非洲或欧洲血统的特定基因组区域，以确定可能与环境暴露哮喘危险因素相互作用的染色体片段。血统和环境暴露风险因素对于哮喘风险至关重要，提出了三个具体目标来检验我们的假设并实现我们提出的计划：目标 1) 使用多种族基因分型阵列确定 AA 哮喘儿童的遗传血统并进行混合图谱；目标 2) 确定当地血统和环境暴露风险因素在改变哮喘风险方面的相互作用；目标 3) 复制最有希望的血统特异性和 A:E 相互作用。 6000 个 SNP 并制定遗传祖先风险评分 (GARS)，以潜在地解释哮喘风险的很大一部分。为了完成这些目标，我们将分析来自辛辛那提儿童医院医疗中心儿科存储库队列的遗传、环境暴露因素、临床和流行病学数据。辛辛那提生物银行。这项研究将利用一项独特的基于血统的研究，提高我们对血统和环境暴露因素（交通、香烟烟雾、霉菌）之间相互作用的理解。通过设计，我们特别有能力制定一个路线图，以阐明遗传和环境暴露差异的相对影响，并揭示少数民族儿童哮喘的病因，这是我们研究的最终目标之一。