Epigenome-wide variations and socio-environmental exposures in African American asthmatic children

非裔美国哮喘儿童的表观基因组变异和社会环境暴露

基本信息

批准号：
10297950
负责人：
Tesfaye B. Mersha
金额：
$ 68.09万
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：
2021
资助国家：
美国
起止时间：
2021-09-24 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297950
关键词：
Address Affect African American Age Air Pollution Algorithms Allergens American Asthma Bioinformatics Biological Biometry Caring Cells Child Childhood Childhood Asthma Clinic Clinical Clinical Sciences Communities Complex DNA Methylation DNA Modification Process DNA methylation profiling Data Disease Environmental Exposure Epigenetic Process European Exposure to Gene Frequency Genetic Genetic Predisposition to Disease Genome Genotype Geography Goals Green space Hypersensitivity Immune Incidence Individual Intervention Link Maps Measures Mediating Mediation Methylation Minority Modeling Neighborhoods Ohio Pathogenesis Pediatrics Phenotype Public Health Research Research Personnel Risk Risk Factors Sampling Science Site Social Characteristics Social Environment Statistical Methods Stress Study models Sum Surrogate Markers System Testing Time Tobacco smoke United States United States National Institutes of Health Variant Violence Work asthma model asthmatic base biobank case control clinical predictors clinical risk cohort deprivation epigenetic variation epigenome epigenome-wide association studies gene function genome wide methylation genome-wide improved indexing innovation insight methylation pattern multi-ethnic non-genetic novel population based predictive marker predictive modeling programs psychosocial racial disparity repository risk prediction risk prediction model risk stratification screening sex social social epidemiology socioeconomics

项目摘要

ABSTRACT Asthma is a major public health problem in the United States, affecting 11 million children. Despite advances in asthma care, African Americans (AAs) are 4 times more likely to be hospitalized and 5 times more likely to die from asthma than European Americans (EAs). Several factors could be responsible for the observed asthma racial disparities including genetic and non-genetic factors. While epigenetics appear to serve as a critical biological switch between genetic vulnerability and socio-environmental exposures, limited studies are available that directly map the socio- environmental exposures with asthmatic epigenome/genome information. In addition, current approach do not leverage existing geospatial data such as environmental exposure and neighborhood socioeconomic conditions to improve asthma risk prediction. In this proposal, we will utilize comprehensive geocoding algorithms, novel statistical methods to integrate social, clinical, environmental, genetic, and epigenetic data into a composite score for asthma risk stratification and prediction. The overall objective of this research is to conduct genome-wide Methyl-Seq analysis and leverage existing well-phenotyped AA pediatric asthma cohort with extensive socio-environmental exposures and ancestry-tailored multi-ethnic genotyping array (MEGA) data from Cincinnati Pediatrics Repository to accurately determine and develop ancestry- specific asthma risk stratification and prediction models. The objective of this application is to undertake an epigenome-wide association study (EWAS), incorporating geocoded neighborhood- and individual-level socio-environmental predictors, and novel analytical strategies to create a composite risk score incorporating methylation risk score (MRS), ancestry, environmental exposures and social characteristics to predict asthma. We will accomplish these objectives through the following Specific Aims: 1) Develop an ancestry-specific methylation risk score (MRS) for asthma and test its association with socio-environmental exposures contributing to asthma risk. 2) Determine the mediation effects of MRS between genetic ancestry and asthma risk. 3) Develop a multivariable risk predictive model for asthma incorporating MRS, genetic ancestry, clinical, and socio-environmental risk factors. The proposed research is innovative because this will be the first time a MRS approach will be used to develop a population-based risk profile in asthmatics. The study will provide insights in the use of risk stratification for screening and targeted interventions. This work is significant because it can serve as a model to study the composite effect of MRS, ancestry, socio-environmental, and clinical risk factors on racial disparities in other well-documented common complex diseases beyond asthma.

抽象的哮喘是美国的一个主要公共卫生问题，影响着 1100 万儿童。尽管随着哮喘护理的进步，非洲裔美国人 (AA) 住院的可能性增加了 4 倍死于哮喘的可能性是欧洲裔美国人 (EA) 的 5 倍。有几个因素可能是造成观察到的哮喘种族差异的原因包括遗传和非遗传因素。虽然表观遗传学似乎是遗传脆弱性和遗传脆弱性之间的关键生物转换。社会环境暴露，可直接绘制社会环境暴露图的研究有限。环境暴露与哮喘表观基因组/基因组信息。此外，目前方法不利用现有的地理空间数据，例如环境暴露和社区社会经济条件以改善哮喘风险预测。在这个提案中，我们将利用综合地理编码算法、新颖的统计方法来整合社交、将临床、环境、遗传和表观遗传数据转化为哮喘风险的综合评分分层和预测。这项研究的总体目标是进行全基因组研究甲基测序分析并利用现有表型良好的 AA 儿科哮喘队列广泛的社会环境暴露和针对祖先的多种族基因分型阵列来自辛辛那提儿科存储库的 (MEGA) 数据，用于准确确定和开发血统- 特定的哮喘风险分层和预测模型。该应用程序的目的是进行全表观基因组关联研究（EWAS），纳入地理编码邻域- 和个人层面的社会环境预测因素，以及新颖的分析策略来创建综合风险评分，包括甲基化风险评分（MRS）、血统、环境暴露和社会特征来预测哮喘。我们将实现这些目标通过以下具体目标： 1) 制定特定祖先的甲基化风险评分 (MRS) 哮喘并测试其与导致哮喘的社会环境暴露的关系风险。 2)确定MRS在遗传血统和哮喘风险之间的中介作用。 3）开发包含 MRS、遗传血统、临床和社会环境危险因素。拟议的研究具有创新性，因为将是首次使用 MRS 方法来制定基于人群的风险概况哮喘患者。该研究将为利用风险分层进行筛查和评估提供见解。有针对性的干预措施。这项工作意义重大，因为它可以作为研究 MRS、血统、社会环境和临床危险因素对种族的综合影响除哮喘外，其他有据可查的常见复杂疾病的差异。