(2 of 2) Genetic Epidemiology of COPD

项目摘要/摘要 慢性阻塞性肺病(COPD)是美国第三大死因， 是一种异质综合征。全面了解COPD的异质性需要纵向 阐明疾病进展的遗传、临床和放射学决定因素的数据。这 提案将通过对所有患者进行为期十年的纵向跟踪访问来延长COPD基因研究 有COPD基因受试者，有后续的胸部CT扫描。COPDgene的主要目标是： A)确定影响COPD和COPD相关表型发生的新的遗传位点； B)将慢性阻塞性肺病重新分类为最终可用于制定有效的特定亚型的亚型 治疗；以及c)将COPD基因中的发现转化为改善诊断和预后 在普通临床人群中治疗慢性阻塞性肺疾病的方法。这次更新的主要假设是 广泛的遗传和纵向表型数据在慢性阻塞性肺疾病或高危人群中的应用 For COPD将能够创建和验证新的COPD分类系统 诊断和预后方面的影响。具体目标是：1)通过以下方式评估COPD的进展 使用临床完成对COPD基因队列中所有可用受试者的十年随访 胸部CT扫描的表型及定量和肉眼分析；2)使用全基因组 对COPD基因队列的测序分析以识别稀有和常见的遗传决定因素 研究COPD亚型的易感性和疾病进展，并创造有效的遗传风险 COPD评分；以及3)将COPD亚型和遗传学的COPD基因发现转化为一般 通过与临床肺癌筛查项目的相互作用，对临床人群进行评估。预计 整个COPD基因队列的全基因组测序分析将通过 TOPMed程序。这些数据结合了十年的纵向临床数据和CT成像 预计队列数据将有助于识别独特COPD的新遗传关联 子类型。长期目标是能够加强诊断、预后和治疗 慢性阻塞性肺疾病个体化治疗的方法。

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.