African American Sarcoidosis Genetics Resource

描述（由申请人提供）： 结节病是一种多器官肉芽肿性炎症性疾病，可能是由遗传易感个体的过度T细胞反应引起的。非裔美国人更频繁和严重地受到结节病的影响，但很少有非裔美国人患者存在。然而，我们已经积累了近3,000名结节病患者、家庭成员和对照的大型、良好表型队列，对这些患者进行了广泛的基因组搜索，以确定潜在的易感基因座。具体来说，这个“大机会”提案将使用一个独特且易于获得的队列，使用第一个也是唯一一个商业化的基因分型产品，在非洲裔美国人中进行第一个也是急需的全基因组关联（GWA）扫描，从而充分覆盖非洲基因组（>85%）。由于我们队列的规模，我们准备在一个独立的样本中复制我们的发现，因此提出候选基因和区域进行进一步表征。我们可以根据已经获得的祖先数据进一步描述这些影响的人群起源。最后，我们将开发一种生物信息学工具，用于储存和调查遗传数据（例如单核苷酸多态性，拷贝数变异等），基因组数据（例如物理位置，基因位置，功能，保守程度等），以及来自先前连锁，混合和候选基因关联研究以及本研究和其他GWA研究的统计数据。该项目与GO机制的目标一致，因为我们可以在获得资金后立即开始，本文中的发现将产生多个后续研究，数据库资源将允许我们的领域迈出下一步，超越关联，进入基于路径和生物信息学驱动的分析，最后，我们将通过购买超过200万美元的国内产品和服务，以及创造和保留一些生物技术和行政工作，来刺激美国的研究企业。总之，我们广泛的非裔美国人队列和我们的基因分型，分析和生物信息学资源以及我们的专家团队在AA结节病遗传学方面的丰富经验使得这种规模和范围的实验不太可能由任何其他小组完成。 公共卫生相关性： 该项目将通过以下方式快速推进结节病以及可能的其他肉芽肿或炎症性疾病的遗传学研究：1）在整个基因组中识别和复制与遗传变异的关联，2）使用相关的统计学，遗传学和基因组学数据促进这些影响的表征。此外，该项目还将为美国生物技术产品和就业带来广泛的收入。

DESCRIPTION (provided by applicant): Sarcoidosis is a multiorgan granulomatus inflammatory disorder likely resulting from an exaggerated T-dell response in genetically susceptible individuals. African-Americans are more frequently and severely affected by Sarcoidosis yet few collections of African American patients exist. We however, have amassed a large, well phenotyped cohort of close to 3,000 Sarcoidosis patients, family members and controls on which to perform an extensive search of the genome to identify potential susceptibility loci. Specifically, this "Grand Opportunity" proposal will, using a unique and easily-accessible cohort, perform the first, and much needed, genome-wide association (GWA) scan in African Americans using the first and only commercially available genotyping product that results in adequate coverage (>85%) of the African genome. Because of the size of our cohort, we are poised to replicate our findings in an independent sample and therefore propose candidate genes and regions for further characterization. We can further characterize the population origin of these effects based on ancestry data already obtained. Finally, we will develop a bioinformatics tool for the repository and investigation of genetic data (e.g. single nucleotide polymorphisms, copy number variants, etc), genomic data (e.g. physical location, genic location, function, degree of conservation, etc), and statistical data from prior linkage, admixture and candidate gene association studies as well as this and other GWA studies. This project aligns with the goals of the GO mechanism in that we can begin immediately upon funding, the discoveries made herein will birth multiple follow-up studies, the database resource will allow our field to take the next step beyond association into pathway-based and bioinformatics-driven analyses and finally, we will stimulate the American research enterprise via the purchase of over $2M in domestically produced goods and services and the creation and retention of several biotech and administrative jobs. In sum, our extensive African American cohort and our genotyping, analysis and bioinformatics resources as well as the extensive experience of our team of experts in AA Sarcoidosis genetics make an experiment of this magnitude and scope very unlikely to be completed by any other group. PUBLIC HEALTH RELEVANCE: This project will fast-forward Sarcoidosis, and likely other granulomatus or inflammatory disorders, genetics research by 1) identifying and replicating association to genetic variants throughout the genome and 2) facilitating characterization of these effects using related statistical, genetics and genomics data. In addition, this project will generate extensive revenue for American biotech products and jobs.