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

• 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
• 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

 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