(1 of 2) Genetic Epidemiology of COPD

项目总结/摘要 慢性阻塞性肺疾病（COPD）是美国第三大死因， 是一种异质性综合征。全面了解COPD异质性需要纵向 阐明疾病进展的遗传、临床和影像学决定因素的数据。这 一项提案将通过对所有患者进行10年的纵向随访来扩展COPD基因研究。 可用的COPD基因受试者，随访胸部CT扫描。COPDGene的主要目标是： a）鉴定影响COPD和COPD相关表型发展的新的遗传基因座; B）将COPD重新分类为亚型，这些亚型最终可用于开发有效的亚型特异性 c）将COPDGene中的发现转化为改善诊断和预后 一般临床人群中COPD的治疗方法。这种更新的主要假设是 应用是在患有COPD或处于风险中的受试者中的广泛遗传和纵向表型数据， 将能够创建和验证一个新的COPD分类系统， 诊断和预后意义。具体目的是：1）通过以下方法评估COPD的进展： 使用临床试验完成COPDGene队列中所有可用受试者的10年随访 表型和胸部CT扫描的定量和视觉分析; 2）使用全基因组 对COPD基因组进行测序分析，以确定罕见和常见的遗传决定因素 COPD亚型的易感性和疾病进展，并产生有效的遗传风险 COPD评分; 3）将COPD基因对COPD亚型和遗传学的发现转化为一般 通过与临床肺癌筛查计划的相互作用，确定临床人群。预计各国 全基因组测序分析将在整个COPDGene队列中完成， TOP计划本资料结合10年纵向临床资料和CT影像 预计队列数据能够识别独特COPD的新遗传关联 亚型长期目标是增强诊断、预后和治疗 COPD的个性化治疗方法。

PROJECT SUMMARY / ABSTRACT Chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, is a heterogeneous syndrome. Comprehensive insight into COPD heterogeneity requires longitudinal data to elucidate the genetic, clinical, and radiographic determinants of disease progression. This proposal will extend the COPDGene Study by performing ten-year longitudinal follow-up visits on all available COPDGene subjects, with follow-up chest CT scans. The primary goals of COPDGene are: a) To identify new genetic loci that influence the development of COPD and COPD-related phenotypes; b) To reclassify COPD into subtypes that can ultimately be used to develop effective subtype-specific therapies; and c) To translate the findings in COPDGene to improve diagnostic and prognostic approaches to COPD in general clinical populations. The primary hypothesis for this renewal application is that extensive genetic and longitudinal phenotypic data in subjects with COPD or at risk for COPD will enable creation and validation of a new classification system for COPD with distinct diagnostic and prognostic implications. The specific aims are: 1) To evaluate progression of COPD by completing a ten-year follow-up of all available subjects in the COPDGene cohort using clinical phenotyping and both quantitative and visual analysis of chest CT scans; 2) To use whole genome sequencing analysis on the COPDGene cohort to identify both rare and common genetic determinants of susceptibility and progression of disease in COPD subtypes and to create effective genetic risk scores for COPD; and 3) To translate COPDGene findings on COPD subtypes and genetics to general clinical populations by interaction with clinical Lung Cancer Screening Programs. It is anticipated that whole genome sequencing analysis will be completed on the entire COPDGene cohort through the TOPMed program. This data in combination with ten-year longitudinal clinical data and CT imaging data on the cohort is expected to enable identification of novel genetic associations for unique COPD subtypes. The long-term goal is to enable enhanced diagnostic, prognostic and therapeutic approaches for personalized therapy in COPD.