INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA
批准号:
8724089
负责人:
Blanca E Himes
金额:
$23.7万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-01 至 2016-06-30
关键词:
AddressAffectAmericanArchitectureAsthmaBiologicalBronchodilator AgentsChronicChronic Obstructive Airway DiseaseClinicalComplexDataData SourcesDevelopmentDiseaseEnvironmentEnvironmental Risk FactorGene ExpressionGenesGeneticGenetic ModelsGenomicsHumanHuman GeneticsHuman GenomeInbred Strains MiceIndividualLeadLung diseasesMachine LearningMapsMethodsModelingMusPathway interactionsPatientsPopulationPredispositionRiskSourceSurveysTestingVariantWorkabstractingairway hyperresponsivenessbasecomputer based statistical methodsgenetic variantgenome wide association studyimprovedinsightmouse developmentmouse genomenovelpredictive modelingprognosticprotein protein interactionresponsetrait
中文摘要
摘要
哮喘是一种慢性呼吸道疾病,影响着2000多万美国人和全球3亿人,
是多种遗传和环境因素复杂相互作用的结果。许多研究
寻找导致哮喘易感性的个体遗传变异,但彻底了解
哮喘的遗传学基础还没有被发现。我们的主要假设是,
通过考虑多个基因并结合
多个基因组数据来源,包括人类哮喘和小鼠气道高反应性(AHR)
数据这一假设将通过具体的目标来解决,我们将:(1)识别遗传变异,
通过在近交系中定位与AHR相关的区域来使人类易患哮喘并调节人类AHR
小鼠品系与人类全基因组关联数据,(2)使用基因表达数据,已知蛋白质-蛋白质
相互作用和已知的功能途径,以加强对哮喘和AHR遗传变异的搜索,
人类,和(3)整合个体人类遗传变异以创建以下多变量预测模型:
哮喘通过特异性目的1和2鉴定的新变体将通过独立的重复验证。
哮喘患者的人群。在特定目标3中创建的预测模型将通过以下方式进行验证:
在独立的哮喘人群中的复制和预测。通过完成具体目标,
我们希望在开发哮喘遗传学的综合模型方面取得进展,
特别是以气道反应性增加为特征的哮喘。
英文摘要
ABSTRACT
Asthma, a chronic respiratory disease affecting over 20 million Americans and 300 million people worldwide,
results from the complex interaction of multiple genetic and environmental factors. Many studies have
searched for individual genetic variants that contribute to asthma susceptibility, but a thorough understanding
of the genetic basis of asthma has not been achieved. Our main hypothesis is that the genetic architecture
underlying asthma susceptibility can be better understood by considering multiple genes and incorporating
multiple sources of genomic data, including human asthma and mouse airways hyperresponsiveness (AHR)
data. This hypothesis will be addressed via specific aims in which we will: (1) identify genetic variants that
predispose humans to asthma and modulate human AHR by mapping regions associated with AHR in inbred
strains of mice to human genome-wide association data, (2) use gene expression data, known protein-protein
interactions, and known functional pathways to enhance the search for asthma and AHR genetic variants in
humans, and (3) integrate individual human genetic variants to create a multivariate predictive model of
asthma. Novel variants identified by Specific Aims 1 and 2 will be validated by replication in independent
human populations of asthmatics. The predictive model created in Specific Aim 3 will be validated through
replication and prediction in independent human populations of asthmatics. By completing the specific aims,
we hope to make progress towards the development of a comprehensive model of the genetics of asthma,
particularly of asthma characterized by increased airways responsiveness.
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会议论文
Precision Approaches to Reduce Asthma Disparities with Electronic Health Record Data
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批准号:10540025
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项目类别:
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资助金额:$81.23万
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财政年份:2022
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负责人:Blanca E Himes
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依托单位:
Precision Approaches to Reduce Asthma Disparities with Electronic Health Record Data
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批准号:10689250
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项目类别:
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资助金额:$79.67万
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财政年份:2022
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负责人:Blanca E Himes
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依托单位:
CEBPD-Mediated Mechanisms of Glucocorticoid Insensitivity in Severe Asthma
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批准号:9914313
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项目类别:
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资助金额:$63.59万
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财政年份:2017
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负责人:Blanca E Himes
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依托单位:
Integrative Genomics Approaches to Model the Genetic Architecture of Asthma
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批准号:8955243
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项目类别:
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资助金额:$16.34万
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财政年份:2014
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负责人:Blanca E Himes
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依托单位:
Integrative Genomics Approaches to Model the Genetic Architecture of Asthma
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批准号:8847988
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项目类别:
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资助金额:$22.11万
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财政年份:2014
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负责人:Blanca E Himes
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依托单位:
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA
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批准号:8727091
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项目类别:
-
资助金额:$8.06万
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财政年份:2013
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负责人:Blanca E Himes
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依托单位:
Translational Research Training Program in Environmental Health Sciences
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批准号:10410778
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项目类别:
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资助金额:$46.25万
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财政年份:2012
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负责人:Blanca E Himes
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依托单位:
Translational Research Training Program in Environmental Health Sciences
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批准号:10636883
-
项目类别:
-
资助金额:$47.65万
-
财政年份:2012
-
负责人:Blanca E Himes
-
依托单位:
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA
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批准号:8299478
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项目类别:
-
资助金额:$13.73万
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财政年份:2011
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负责人:Blanca E Himes
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依托单位:
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA
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批准号:8189641
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项目类别:
-
资助金额:$13.78万
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财政年份:2011
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负责人:Blanca E Himes
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依托单位:
Exposure Biology Informatics Facility Core
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批准号:10189590
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项目类别:
-
资助金额:$15.12万
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财政年份:2006
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负责人:Blanca E Himes
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依托单位:
Exposure Biology Informatics Facility Core
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批准号:10606573
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项目类别:
-
资助金额:$14.32万
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财政年份:2006
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负责人:Blanca E Himes
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依托单位:
Exposure Biology Informatics Facility Core
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批准号:10381530
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项目类别:
-
资助金额:$14.64万
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财政年份:2006
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负责人:Blanca E Himes
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依托单位:
海外基金