Systematic Review and Meta-Analysis of COPD Genetic Studies

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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.