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Study Description

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, one called Freeze 4 (GRCh37) and another called Freeze 5b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 4, Phase 1" and "TOPMed Whole Genome Sequencing Project - Freeze 5b, Phases 1 and 2". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project collected a set of extended pedigrees ascertained through subjects with severe, early-onset COPD. This study has enrolled subjects with severe COPD (forced expiratory volume in one second (FEV1) < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and candidate gene association analysis. Approximately 80 of the severe, early-onset COPD probands will undergo whole genome sequencing in this project with sequencing data available through dbGaP.

  • This third study release makes available VCF files derived from sequence aligned to genome build 38, in addition to those aligned to build 37 and available through study version 1. The samples in the b38 vs b37 VCF may also differ.

  • Study Weblink: Boston COPD
  • Study Type: Pedigree Whole Genome Sequencing
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 80

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

COPD Probands:
Inclusion Criteria
Age at Enrollment: < 53 years
Pre-bronchodilator FEV1 ≤ 40% predicted)
Physician-diagnosed COPD
Exclusion Criteria
Severe alpha-1 antitrypsin deficiency
Concomitant respiratory disorder other than asthma or COPD (such as, but not limited to, diffuse bronchiectasis, cystic fibrosis, or interstitial lung disease)
Lung surgery with removal of a lobe or more (including lung volume reduction surgery or lung transplantation) unless preoperative pulmonary function tests are available

Relatives of EOCOPD Probands
Inclusion Criteria
Age at enrollment: 10 years or greater
First or second-degree relative of an EOCOPD proband, or first-degree relative of another affected pedigree member
Exclusion Criteria
Severe alpha-1 antitrypsin deficiency
Concomitant respiratory disorder other than asthma or COPD (such as, but not limited to, diffuse bronchiectasis, cystic fibrosis, or interstitial lung disease)
Lung surgery with removal of a lobe or more (including lung volume reduction surgery or lung transplantation) unless preoperative pulmonary function tests are available

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq X Ten N/A N/A
Study History

The Boston Early-Onset COPD was started in 1994 in an effort to find genetic determinants of COPD other than alpha-1 antitrypsin deficiency. This study has been funded by a series of grants from the NHLBI, most recently by R01 HL113264 (MPIs: Edwin K. Silverman and Michael H. Cho) and by an administrative supplement to R01 HL089856 (PI: Edwin K. Silverman).

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution