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)： 在美国，哮喘影响着1700多万人，是发病的一个重要原因。 开发减轻哮喘负担的新疗法是科学界的主要优先事项，但此类研究往往受到用于研究的临床相关生物样本有限的阻碍。这项建议的主要目标是建立哮喘综合基因组研究的生物资料库，这是一个开放获取的永生化细胞系、cDNA和DNA的集合，并附带一个针对这些样本的补充数据集，其中包括广泛的表型数据，以及来自参与正在进行的哮喘遗传和基因组研究的2700多名特征良好的受试者的全基因组SNP基因、基因表达和甲基化数据。这个哮喘生物资料库将通过Eve Consortium建立，这是一个由来自11个学术中心的美国研究人员组成的合作努力，他们已经对哮喘进行了全基因组关联研究(GWAS)。EVE队列总共有3万多名受试者，拥有全基因组的SNP数据，并提供了北美哮喘人群的广泛代表性。哮喘生物储存库将通过以下三个具体目标开发。在具体目标1中，将收集血液样本和与哮喘相关的初级细胞类型(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)，用于基因表达谱和DNA甲基化研究。淋巴母细胞系也将建立起来。具体目标2侧重于开发一个附带的数据库，其中包括所有收集的样本的全基因组基因表达和DNA甲基化情况 25%的永生化细胞系，以便于进行全面的整合基因组分析。该数据库将链接到临床和全基因组的基因数据(在数据库GaP中)，并与收集的生物标本和细胞系一起，将哮喘生物资料库的全部提交给NHLBI生物标本资料库和数据资料库信息协调中心(BioLINCC)，以便分发给科学界。特殊目标3将使用开发的数据库进行全面的综合基因组分析，以确定对哮喘发病机制至关重要的调节基因变异。这些研究将包括哮喘严重程度的表达谱；全基因组表达数量性状(EQTL)定位；跨哮喘相关组织的基因表达谱和已识别的eQTL的比较；以及哮喘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，并与哮喘生物信息库数据库连接，为研究人员提供未来研究的初步候选基因座。哮喘综合基因组研究生物资料库将是世界上与哮喘相关的生物材料和基因组数据的最大集合，也是世界各地哮喘研究人员的宝贵资源。 (摘要结束)