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: 9905418
• 负责人: Tesfaye B. Mersha
• 金额: $ 65.3万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905418
• 关键词: Address; Admixture; Affect; African; African American; Age; Asthma; Biological; 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; ancestry analysis; asthmatic; base; biobank; cigarette smoke; cohort; conditioning; design; epidemiologic data; gene environment interaction; genetic architecture; genome wide association study; genome-wide; improved; innovation; insight; minority children; novel; programs; public health intervention; public health relevance; repository; risk prediction model; 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

 描述（由适用提供）：这项拟议的研究的目的是确定非裔美国人（AA）受试者的哮喘风险程度在多大程度上是通过环境暴露风险因素来改变的。最近的研究确定了导致哮喘风险的遗传和环境暴露因素。但是，这些因素解释一个人哮喘的风险的程度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，这将导致对AA儿童中遗传血统与哮喘的环境原因之间的复杂相互作用的深入了解，并确定此信息的实用性，以预测和减少AA儿童哮喘风险。尽管哮喘护理的进展，AAS住院的可能性是哮喘的可能性高四倍，而不是非AAS。 AA具有不同比例的父母基因组的贡献，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，以鉴定可能与环境暴露哮喘风险因素相互作用的染色体片段。我们假设祖先和环境暴露风险因素对哮喘风险至关重要。提出了三个特定的目的来检验我们的假设并实现我们的计划：目标1）确定使用多种族基因分型阵列的AA哮喘儿童的遗传血统和进行混合映射；目标2）在改变哮喘风险时确定地方血统与环境暴露风险因素之间的相互作用；目标3）复制最有前途的祖先特异性和A：E相互作用6000 SNP，并发展遗传祖先风险评分（GARS），以可能解释大部分哮喘风险。为了完成这些目标，我们将分析辛辛那提儿童医院医疗中心儿科储存库同伙和辛辛那提生物银行的遗传，环境暴露因素，临床和流行病学数据。这项研究将提高我们对祖先和环境暴露因素（交通，香烟烟，霉菌）之间相互作用的理解，这些因素改变了哮喘的风险。使用基于祖先的独特研究设计，我们尤其适合开发路线图，以揭示遗传和环境暴露差异的相对贡献，并揭示少数民族儿童哮喘的病因。预测哮喘的发展或进展是我们研究的最终目标之一。 1

项目成果

The Utility of Resolving Asthma Molecular Signatures Using Tissue-Specific Transcriptome Data.

• DOI: 10.1534/g3.120.401718
• 发表时间: 2020-11-05
• 期刊: G3 (Bethesda, Md.)
• 作者: Ghosh D;Ding L;Bernstein JA;Mersha TB
• 通讯作者: Mersha TB

Every contact leaves a trace: contact with the criminal justice system, life outcomes, and the intersection with genetics.

每一次接触都会留下痕迹：与刑事司法系统的接触、生活结果以及与遗传学的交叉。

• DOI: 10.1016/j.copsyc.2018.09.008
• 发表时间: 2019
• 期刊: Current opinion in psychology
• 影响因子: 5.9
• 作者: Motz,RyanT;Tanksley,Peter;Liu,Hexuan;Mersha,TesfayeB;Barnes,JC
• 通讯作者: Barnes,JC

AllergyGenDB: A literature and functional annotation-based omics database for allergic diseases.

AllergyGenDB：基于文献和功能注释的过敏性疾病组学数据库。

• DOI: 10.1111/all.14219
• 发表时间: 2020
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Chen,Siqi;Ghandikota,Sudhir;Gautam,Yadu;Mersha,TesfayeB
• 通讯作者: Mersha,TesfayeB

Environmental Determinants of Coronavirus Disease 2019 (COVID-19).

• DOI: 10.1007/s11882-021-00993-1
• 发表时间: 2021-03-05
• 期刊: Current allergy and asthma reports
• 影响因子: 5.5
• 作者: Brandt EB;Mersha TB
• 通讯作者: Mersha TB

The social, economic, political, and genetic value of race and ethnicity in 2020.

• DOI: 10.1186/s40246-020-00284-2
• 发表时间: 2020-10-15
• 期刊: Human genomics
• 影响因子: 4.5
• 作者: Mersha TB;Beck AF
• 通讯作者: Beck AF