Systematic Review and Meta-Analysis of COPD Genetic Studies

描述(申请人提供)：慢性阻塞性肺病是美国第四大死因，也是全球第五大常见死因。人类遗传变异知识的快速增长为COPD的新治疗方法和更准确的风险预测工具带来了希望。由于可用于COPD关联测试的大量遗传数据，开发一个公共可访问的研究基础设施来访问、组织和合成遗传关联数据非常重要。作为完成这项任务的手段之一，人类基因组流行病学网络强调需要针对疾病定期更新遗传关联研究的系统评价和荟萃分析。该提案将对文献进行全面检索，以便：1.)对所有已发表的常见基因变异和慢性阻塞性肺病研究进行详细的描述性评估。2.)对在三个或更多独立研究群体中研究的遗传基因座进行定量荟萃分析。3.)制作人类基因组的可视化地图，表示所进行的研究的数量和报告的特定基因组领域的积极关联的数量。利用从描述性评估中收集的数据，我们将量化研究间遗传效应大小的异质性，并确定这种异质性的原因。我们还将把一项悬而未决的全基因组关联研究(COPD首批此类研究之一)的原始数据纳入荟萃分析和可视化地图。该项目将完成所需的初步工作，以建立一个在线的、可公开获得的慢性阻塞性肺疾病遗传关系简编，类似于先前存在的其他复杂疾病的网站，如阿尔茨海默病和糖尿病基因。开发一个在线的、公开可用的数据库来汇编和合成COPD基因研究的信息，将是COPD研究界的一个重大好处，并将有助于完成NHLBI的使命之一，即促进有助于改进COPD预防、诊断和治疗的研究。公共卫生相关性：拟议的研究将为COPD遗传学研究领域提供必要的基础设施。这将有助于目前识别慢性阻塞性肺疾病的遗传原因的努力。了解这些遗传原因将带来更好的COPD治疗方法。

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.