Genetic Epidemiology of COPD (COPDGene)

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project will establish a racially diverse cohort that is sufficiently large and appropriately designed for genome-wide association analysis of COPD. A total of 10,000 subjects will be recruited, including control smokers, definite COPD cases (GOLD Stage 2 to 4), and subjects not included in either group (GOLD 1 or GOLD-Unclassified). This cohort will be used for cross-sectional analysis, although long-term longitudinal follow-up will be a future goal. The primary focus of the study will be genome-wide association analysis to identify the genetic risk factors that determine susceptibility for COPD and COPD-related phenotypes. Detailed phenotyping of both cases and controls, including chest CT scan assessment of emphysema and airway disease, will allow identification of genetic determinants for the heterogeneous components of the COPD syndrome. **The hypotheses to be studied are: 1) Precise phenotypic characterization of COPD subjects using computed tomography, as well as clinical and physiological measures, will provide data that will enable the broad COPD syndrome to be decomposed into clinically significant subtypes. 2) Genome-wide association studies will identify genetic determinants for COPD susceptibility that will provide insight into clinically relevant COPD subtypes. 3) Distinct genetic determinants influence the development of emphysema and airway disease.** The initial phase of genome-wide association analysis included 500 COPD cases and 500 control subjects (all non-Hispanic White) genotyped with the Illumina Omni-1 chip. The second phase genotyped the entire study cohort using the Illumina Omni-Express chip. Unique aspects of the study include: 1) Inclusion of large numbers of African American subjects (approximately 1/3 of the cohort); 2) Obtaining chest CT scans (including inspiratory and expiratory images); and 3) Inclusion of the full range of disease severity.

**The COPDGene_v6 Cohort is utilized in the following dbGaP sub-studies.** To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" section of this top-level study page phs000179 COPDGene_v6 Cohort. - [phs000296](./study.cgi?study_id=phs000296) ESP LungGO COPDGene - [phs000765](./study.cgi?study_id=phs000765) COPDGene_Geno

慢性阻塞性肺疾病（Chronic obstructive pulmonary disease, COPD）是美国第四大致死性疾病，也是唯一一种发病率持续攀升的主要死亡原因。本项目将构建一个种族多元化队列，样本规模充足且设计合理，可用于开展全基因组关联分析（genome-wide association analysis）。本研究计划招募总计10000名受试者，涵盖吸烟对照人群、确诊慢性阻塞性肺疾病患者（GOLD（Global Initiative for Chronic Obstructive Lung Disease）分期2~4期）以及未归入上述两组的受试者（GOLD 1期或未分类GOLD病例）。尽管长期纵向随访是未来的研究目标，但本队列当前主要用于横断面分析。本研究的核心聚焦于全基因组关联分析，以明确决定慢性阻塞性肺疾病易感性及相关表型的遗传风险因素。对病例组与对照组均开展详细的表型分型，包括通过胸部CT（computed tomography, CT）评估肺气肿与气道疾病，这将助力识别慢性阻塞性肺疾病综合征异质性组分的遗传决定因素。
**本研究拟验证的假说如下：1. 借助计算机断层扫描（computed tomography, CT）、临床及生理学指标对慢性阻塞性肺疾病受试者进行精准表型分型，可将宽泛的慢性阻塞性肺疾病综合征拆解为具有临床意义的亚型；2. 全基因组关联研究可识别慢性阻塞性肺疾病易感性的遗传决定因素，从而为临床相关的慢性阻塞性肺疾病亚型提供研究视角；3. 不同的遗传决定因素分别影响肺气肿与气道疾病的发生发展。**
全基因组关联分析的第一阶段纳入500例慢性阻塞性肺疾病病例与500例对照受试者（均为非西班牙裔白人），使用Illumina Omni-1芯片完成基因分型。第二阶段则采用Illumina Omni-Express芯片对全部研究队列进行基因分型。本研究的独特优势包括：1. 纳入大量非裔美国受试者（约占队列总人数的1/3）；2. 获取胸部CT扫描影像（包括吸气相与呼气相图像）；3. 覆盖全范围的疾病严重程度分层。
**COPDGene_v6队列已被应用于以下dbGaP（Database of Genotypes and Phenotypes）子研究**。若要查看这些子研究中收集的基因型数据、其他分子数据及衍生变量，请点击下述子研究链接，或点击本顶层研究页面（phs000179 COPDGene_v6队列）的“子研究”板块。
- [phs000296](./study.cgi?study_id=phs000296) ESP LungGO COPDGene
- [phs000765](./study.cgi?study_id=phs000765) COPDGene_Geno