Systematic Review and Meta-Analysis of COPD Genetic Studies

描述（由申请人提供）：COPD是美国第四大死亡原因，也是全球第五大最常见死亡原因。人类遗传变异知识的迅速增加为COPD的新治疗和更准确的风险预测工具提供了希望。随着大量的遗传数据可用于COPD关联测试，重要的是要开发一个公开访问的研究基础设施，用于访问，组织和合成遗传关联数据。作为完成这一任务的一种手段，人类基因组流行病学网络强调需要对特定疾病进行定期更新的系统评价和遗传关联研究的荟萃分析。本提案将对文献进行全面检索，以便：1.）对所有已发表的常见遗传变异和COPD研究进行详细的描述性评估。2.）的情况。对在三个或更多独立研究人群中研究的遗传位点进行定量荟萃分析。3.）第三章制作人类基因组的可视化地图，代表所进行的研究数量和特定基因组区域报告的阳性关联数量。使用从描述性评估中收集的数据，我们将量化遗传效应大小的研究间异质性，并确定这种异质性的原因。我们还将把一项正在进行的全基因组关联研究（COPD首批此类研究之一）的主要数据纳入荟萃分析和视觉地图中。该项目将完成建立一个在线、公开的COPD遗传关联概要所需的初步工作，类似于其他复杂疾病（如AlzGene和PDGene）的现有网站。开发一个在线的、公开的数据库来汇编和综合来自COPD遗传学研究的信息，将是COPD研究界的一个主要受益者，并将有助于实现NHLBI的使命之一，即促进研究，以改善COPD的预防、诊断和治疗。公共卫生相关性：拟议的研究将为COPD遗传学研究领域提供所需的基础设施。这将有助于目前确定COPD遗传原因的努力。了解这些遗传原因将有助于更好地治疗COPD。

DESCRIPTION (provided by applicant): COPD is the fourth leading cause of the death in the United States and the fifth most common cause of death worldwide. The rapidly increasing knowledge of human genetic variation offers hope for new treatments and more accurate risk prediction tools for COPD. With the large volume of genetic data available for COPD association testing, it is important to develop a publicly accessible research infrastructure for accessing, organizing, and synthesizing genetic association data. As one means of accomplishing this task, The Human Genome Epidemiology Network has emphasized the need for disease specific, regularly updated systematic reviews and meta-analyses of genetic association studies. This proposal will conduct a comprehensive search of the literature in order to: 1.) Conduct a detailed descriptive assessment of all published studies of common genetic variants and COPD. 2.) Perform a quantitative meta-analysis of genetic loci studied in three or more independent study populations. 3.) Produce visual maps of the human genome representing the amount of research performed and the number of positive associations reported for particular genomic areas. Using data gathered from the descriptive assessment, we will quantify between-study heterogeneity in genetic effect size and identify causes of this heterogeneity. We will also incorporate primary data from a pending genome-wide association study (one of the first such studies in COPD) into the meta-analysis and visual maps. This project will accomplish the initial work required to establish an online, publicly available compendium of COPD genetic associations similar to preexisting websites for other complex diseases such as AlzGene and PDGene. The development of an online, publicly available database to compile and synthesize information from COPD genetic studies will be a major benefit to the COPD research community, and will help to fulfill one of the missions of the NHLBI to promote research leading to improved prevention, diagnosis, and treatment of COPD. PUBLIC HEALTH RELEVANCE: The proposed research will provide needed infrastructure for the research field of COPD genetics. It will aid current efforts to identify the genetic causes of COPD. Understanding these genetic causes will lead to better treatments for COPD.