Genome Wide Association for Asthma and Lung Function

哮喘和肺功能的全基因组关联

• 批准号: 7576119
• 负责人: Deborah A. Meyers
• 金额: $ 172.41万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-05 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576119
• 关键词: Adult; Affect; African; African American; Asthma; Caucasians; Caucasoid Race; Chicago; Child; Chromosome Mapping; Complex; Data; Data Analyses; Development; Disease; Disease Progression; Disease susceptibility; Environmental Exposure; European; Family; Follow-Up Studies; Frequencies; Funding; Future; Gene Frequency; General Population; Genes; Genetic; Genetic Variation; Genotype; Inheritance Patterns; Lead; Malignant neoplasm of prostate; Maps; Methods; National Heart, Lung, and Blood Institute; Phenotype; Population; Predisposition; Research; Research Personnel; Respiratory physiology; Risk; Sampling; Single Nucleotide Polymorphism; Universities; Work; abstracting; case control; cohort; data management; experience; forest; genetic analysis; genetic variant; genome wide association study; member; method development; novel; novel strategies; prevent; programs; success; trait

DESCRIPTION (provided by applicant): We propose to perform a genome-wide association study (GWA) to identify genetic variation affecting susceptibility to asthma and related quantitative phenotypes using a panel of > 500,000 single nucleotide polymorphisms (SNPs) in case/control U.S. samples of European descent and U.S. samples of African descent with following specific aims 1) To genotype 800 cases with asthma and 600 controls without asthma of European descent and 700 cases with asthma and 450 controls without asthma of African-Americans using the Illumina HumanHap550 BeadChip platform; 2) To conduct both standard and novel genetic analyses to map genes associated with asthma and related quantitative phenotypes such as level of lung function; 3) To conduct follow-up studies in similar samples for asthma and related quantitative phenotypes. Our proposal is unique and significant for the following reasons: 1) Our cohort ascertained through the Severe Asthma Research Program represents the largest number of asthmatics with more severe disease available for genetic studies. 2) Our cohort consists of asthmatics ranging from mild to severe disease representing an excellent opportunity to study quantitative traits such as level of lung function. In addition, our population consists of adult asthmatics, which is important because children with asthma, in general, still have relatively normal lung function. Likewise, the normal (non asthmatic) population does not show the range of level of lung function present in our asthma cohorts. 3) We believe that it is crucial to include African-Americans in the primary genotyping set because of the frequency of asthma in this population and general lack of replication of studies of 'asthma' genes observed in the Caucasian population in African- Americans. This may be due to differences in allele frequencies compounded by differences in environmental exposures. 4) We have assembled a strong collaborative team by joining forces with our long term collaborators at the University of Chicago (we have worked together on the genetics of asthma for over 12 years). Our collaborators at University of Chicago including Dr Nancy Cox recently competed successfully for funding through NHLBI RFA HL-05-011 and will be one of 11 groups in the ENDGAME (ENhancing Data analysis for Genome-wide Association MEthods) consortium developing methods for GWA mapping. We expect that identification of the genes and the specific genetic variants that contribute to the development of asthma and related phenotypes will lead to new approaches for preventing and treating (thus preventing progression) this common, complex disease. (End of Abstract)

描述(由申请人提供)： 我们建议进行一项全基因组关联研究(GWA)，以确定影响哮喘易感性的基因变异和相关的数量表型，使用一组&gt；500,000个单核苷酸多态(SNPs)在病例/对照美国欧洲血统样本和美国非洲裔样本中进行，具体目标如下：1)使用Illumina HumanHap550 BeadChip平台对800名欧洲裔哮喘患者和600名非裔美国人哮喘患者和600名对照人员以及700名非裔美国人的哮喘患者和450名非裔美国人对照进行基因分型；2)进行标准和新颖的基因分析，以绘制与哮喘相关的基因和相关的定量表型，如肺功能水平；3)对类似样本进行哮喘及相关定量表型的随访研究。我们的建议独一无二，意义重大，原因如下：1)我们通过重症哮喘研究计划确定的队列代表了可用于基因研究的患有更严重疾病的哮喘患者的最大数量。2)我们的队列包括从轻度到重度的哮喘患者，这是研究肺功能水平等数量性状的绝佳机会。此外，我们的人口由成年哮喘患者组成，这一点很重要，因为患有哮喘的儿童总体上仍有相对正常的肺功能。同样，正常(非哮喘)人群没有显示出我们哮喘队列中存在的肺功能水平的范围。3)我们认为，将非洲裔美国人包括在主要基因分型集中是至关重要的，因为这一群体中哮喘的频率很高，而且普遍缺乏在高加索人群中观察到的非裔美国人哮喘基因的重复研究。这可能是由于等位基因频率的差异以及环境暴露的差异造成的。4)我们与芝加哥大学的长期合作伙伴联手组建了一个强大的合作团队(我们在哮喘的遗传学方面已经合作了12年以上)。我们在芝加哥大学的合作者，包括Nancy Cox博士，最近通过NHLBI RFA HL-05-011成功地竞争了资金，并将成为EndGame(增强基因组范围关联方法的数据分析)财团开发GWA图谱方法的11个小组之一。我们预计，识别导致哮喘和相关表型发展的基因和特定的遗传变异将导致预防和治疗(从而防止进展)这种常见的复杂疾病的新方法。(摘要结束)

项目成果

Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort.

• DOI: 10.3109/02770903.2016.1158268
• 发表时间: 2016-10
• 期刊: The Journal of asthma : official journal of the Association for the Care of Asthma
• 作者: Li X;Hawkins GA;Moore WC;Hastie AT;Ampleford EJ;Milosevic J;Li H;Busse WW;Erzurum SC;Kaminski N;Wenzel SE;Bleecker ER;Meyers DA
• 通讯作者: Meyers DA

eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS-identified asthma genes.

支气管上皮细胞和支气管肺泡灌洗剂GWAS鉴定的哮喘基因的EQTL。

• DOI: 10.1111/all.12683
• 发表时间: 2015-10
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Li X;Hastie AT;Hawkins GA;Moore WC;Ampleford EJ;Milosevic J;Li H;Busse WW;Erzurum SC;Kaminski N;Wenzel SE;Meyers DA;Bleecker ER
• 通讯作者: Bleecker ER