The Asthma BioRepository for Integrative Genomics Research

用于综合基因组学研究的哮喘生物存储库

• 批准号: 7939844
• 负责人: Benjamin Alexander Raby
• 金额: $ 423.62万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7939844
• 关键词: Affect; Alveolar Macrophages; American; Asthma; Biocompatible Materials; Biological; Biopsy Specimen; Blood specimen; CD4 Positive T Lymphocytes; Cell Line; Classification; Clinical; Collection; Communities; Complementary DNA; Complex; DNA; DNA Methylation; Data; Data Set; Databases; Development; Disease; Environmental Tobacco Smoke; Epigenetic Process; Epithelial Cells; Ethnic Origin; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genetic; Genetic Variation; Genomics; Genotype; Histocompatibility Testing; Human; Immune; Investigation; Link; Lung; Machine Learning; Maps; Methods; Methylation; Molecular; Molecular Analysis; Molecular Profiling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Natural History; Participant; Pathogenesis; Pattern; Peripheral Blood Lymphocyte; Peripheral Blood Mononuclear Cell; Pharmacogenetics; Phenotype; Population; Population Heterogeneity; Predisposition; Quantitative Trait Loci; RNA; Research; Research Personnel; Resources; SNP genotyping; Sampling; Severities; Site; Smooth Muscle; Source; Specimen; Testing; Tissues; Tobacco Smoke Pollution; United States; Variant; abstracting; biobank; bronchial epithelium; cell type; clinically relevant; cohort; database of Genotypes and Phenotypes; genome wide association study; genome-wide; immortalized cell; novel; peripheral blood; repository; sample collection; trait

DESCRIPTION (provided by applicant): Asthma affects over 17 million people in the United States, and is a significant cause of morbidity. Development of novel therapies to reduce asthma burden is a major priority of the scientific community, yet such studies are often hampered by the limited availability of clinically relevant biologic samples for investigation. The primary objective of this proposal is to establish the Asthma BioRepository for Integrative Genomic Research, an open-access collection of immortalized cell lines, cDNA and DNA, and an accompanying complementary dataset for these samples consisting of extensive phenotype data, and genome-wide SNP genotype, gene expression, and methylation data from more than 2,700 well-characterized subjects participating in ongoing genetic and genomic studies of asthma. This Asthma BioRepository will be established through the EVE Consortium, a collaborative effort consisting of U.S. investigators from 11 academic centers who have conducted genome-wide association studies (GWAS) of asthma. The EVE cohorts together total more than 30,000 subjects with genome-wide SNP data and provide broad representation of the North American asthmatic population. The Asthma BioRepository will be developed through the following three Specific Aims. In Specific Aim 1, blood samples and asthma-relevant primary cell types (including CD4+ peripheral blood lymphocytes, peripheral blood mononuclear cells, alveolar macrophages, and lung biopsy specimens) will be collected for gene expression profiling and DNA methylation studies. Lymphoblastic cell lines will also established. Specific Aim 2 focuses on the development of an accompanying database consisting of genome-wide gene expression and DNA methylation profiles for all of the collected samples and 25% of the immortalized cell lines to facilitate comprehensive integrative genomic analysis. This database will be linked to clinical and genome-wide genotype data (in dbGAP), and together with the collected biological specimens and cell lines, the totality of the Asthma BioRepository will be submitted to the NHLBI Biologic Specimen Repository and Data Repository Information Coordinating Center (BioLINCC) for distribution to the scientific community. Specific Aim 3 will use the developed database to perform comprehensive integrative genomic analyses to identify the regulatory genetic variation critical to asthma pathogenesis. These studies will include expression profiling of asthma severity; genome-wide expression quantitative trait (eQTL) mapping; comparison of gene expression profiles and identified eQTLs across asthma-relevant tissues; and genomewide association studies of methylation patterns in asthma. Results of these studies will be submitted to dbGAP and linked to the Asthma BioRepository database to provide investigators with preliminary candidate loci for future investigation. The Asthma BioRepository for Integrative Genomic Research will represent the largest collection of asthma-related biological materials and genomic data in the world, and an invaluable resource for asthma researchers everywhere. (End of Abstract)

描述（由申请人提供）： 哮喘在美国影响超过1700万人，这是发病率的重要原因。 减轻哮喘负担的新型疗法的发展是科学界的主要优先事项，但是这种研究通常会受到临床相关生物样品的可用性有限的研究而阻碍。 The primary objective of this proposal is to establish the Asthma BioRepository for Integrative Genomic Research, an open-access collection of immortalized cell lines, cDNA and DNA, and an accompanying complementary dataset for these samples consisting of extensive phenotype data, and genome-wide SNP genotype, gene expression, and methylation data from more than 2,700 well-characterized subjects participating in ongoing genetic and genomic哮喘的研究。这种哮喘生物座席将通过夏娃财团建立，这是一项合作努力，由来自11个学术中心的美国调查人员组成，这些学术中心已经进行了全基因组协会研究（GWAS）的哮喘。夏娃共同共同将30,000多名受试者与全基因组SNP数据共同提供，并为北美哮喘人群提供广泛的代表。哮喘生物座席将通过以下三个特定目标开发。在特定的目标1中，将收集血液样本和与哮喘相关的原发性细胞类型（包括CD4+外周血淋巴细胞，外周血单核细胞，肺泡巨噬细胞和肺活检标本），以进行基因表达谱和DNA甲基化研究。还将建立淋巴细胞细胞系。具体目标2的重点是开发伴随的数据库，该数据库由全基因组基因表达和所有收集的样品和DNA甲基化谱和DNA甲基化谱和 25％的永生细胞系可促进全面的综合基因组分析。该数据库将与临床和全基因组全基因型数据（在DBGAP中）以及收集的生物样品和细胞系有关，哮喘生物座的总数将提交给NHLBI生物样品的存储库存储库和数据循环信息共同信息协调中心（Biolincc），以分配科学群体。具体目标3将使用开发的数据库进行全面的整合基因组分析，以识别对哮喘发病机理至关重要的调节遗传变异。这些研究将包括哮喘严重程度的表达分析。全基因组表达定量性状（EQTL）映射；比较基因表达谱并鉴定出与哮喘相关组织的EQTL的比较；哮喘中甲基化模式的全基因组关联研究。这些研究的结果将提交给DBGAP，并与哮喘生物座位数据库相关联，以向研究人员提供初步的候选基因座，以供将来进行研究。用于综合基因组研究的哮喘生物措施将代表世界上与哮喘相关的生物学材料和基因组数据的最大收集，也是各地哮喘研究人员的宝贵资源。 （抽象的结尾）