Genetic Epidemiology of COPD (COPDGene) Study Design

Overview

Journal COPD

Publisher Informa Healthcare

Specialty Pulmonary Medicine

Date 2010 Mar 11

PMID 20214461

Citations 806

Authors

Elizabeth A Regan

John E Hokanson

James R Murphy

Barry Make

David A Lynch

Terri H Beaty

Douglas Curran-Everett

Edwin K Silverman

James D Crapo

Affiliations

Soon will be listed here.

Abstract

Background: COPDGene is a multicenter observational study designed to identify genetic factors associated with COPD. It will also characterize chest CT phenotypes in COPD subjects, including assessment of emphysema, gas trapping, and airway wall thickening. Finally, subtypes of COPD based on these phenotypes will be used in a comprehensive genome-wide study to identify COPD susceptibility genes.

Methods/results: COPDGene will enroll 10,000 smokers with and without COPD across the GOLD stages. Both Non-Hispanic white and African-American subjects are included in the cohort. Inspiratory and expiratory chest CT scans will be obtained on all participants. In addition to the cross-sectional enrollment process, these subjects will be followed regularly for longitudinal studies. A genome-wide association study (GWAS) will be done on an initial group of 4000 subjects to identify genetic variants associated with case-control status and several quantitative phenotypes related to COPD. The initial findings will be verified in an additional 2000 COPD cases and 2000 smoking control subjects, and further validation association studies will be carried out.

Conclusions: COPDGene will provide important new information about genetic factors in COPD, and will characterize the disease process using high resolution CT scans. Understanding genetic factors and CT phenotypes that define COPD will potentially permit earlier diagnosis of this disease and may lead to the development of treatments to modify progression.

Citing Articles

TriSwinUNETR lobe segmentation model for computing DIR-free CT-ventilation.

Nomura G, Luong A, Prakash A, Alemand A, Bhowmick T, Ali A Front Oncol. 2025; 15:1475133.

PMID: 40034599 PMC: 11872890. DOI: 10.3389/fonc.2025.1475133.

Identifying chronic obstructive pulmonary disease subtypes using multi-trait genetics.

Ziyatdinov A, Hobbs B, Kanaan-Izquierdo S, Moll M, Sakornsakolpat P, Shrine N EBioMedicine. 2025; 113:105609.

PMID: 40010152 PMC: 11905855. DOI: 10.1016/j.ebiom.2025.105609.

SEVERITY OF LUNG OBSTRUCTION AND OLDER AGE, BUT NOT PHYSICAL ACTIVITY, PREDICT LOCOMOTOR MUSCLE OXIDATIVE IMPAIRMENT IN COPD.

Adami A, Duan F, Calmelat R, Chen Z, Casaburi R, Rossiter H medRxiv. 2025; .

PMID: 39974145 PMC: 11838953. DOI: 10.1101/2025.01.28.25321301.

Classifying COVID-19 hospitalizations in epidemiology cohort studies: The C4R study.

Oelsner E, Krishnaswamy A, Rustamov R, Balte P, Ali T, Allen N PLoS One. 2025; 20(2):e0316198.

PMID: 39928595 PMC: 11809881. DOI: 10.1371/journal.pone.0316198.

Novel risk loci encompassing genes influencing STAT3, GPCR, and oxidative stress signaling are associated with co-morbid GERD and COPD.

Wilson A, Rocco A, Chiles J, Srinivasasainagendra V, Labaki W, Meyers D PLoS Genet. 2025; 21(2):e1011531.

PMID: 39919125 PMC: 11805425. DOI: 10.1371/journal.pgen.1011531.

References

Hoyert D, Arias E, Smith B, MURPHY S, Kochanek K . Deaths: final data for 1999. Natl Vital Stat Rep. 2001; 49(8):1-113. View

Wilk J, Chen T, Gottlieb D, Walter R, Nagle M, Brandler B . A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet. 2009; 5(3):e1000429. PMC: 2652834. DOI: 10.1371/journal.pgen.1000429. View

Pillai S, Ge D, Zhu G, Kong X, Shianna K, Need A . A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009; 5(3):e1000421. PMC: 2650282. DOI: 10.1371/journal.pgen.1000421. View

Silverman E . Exacerbations in chronic obstructive pulmonary disease: do they contribute to disease progression?. Proc Am Thorac Soc. 2007; 4(8):586-90. PMC: 2647649. DOI: 10.1513/pats.200706-068TH. View

McCloskey S, Patel B, Hinchliffe S, Reid E, Wareham N, Lomas D . Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med. 2001; 164(8 Pt 1):1419-24. DOI: 10.1164/ajrccm.164.8.2105002. View

Gottlieb D, Wilk J, Harmon M, Evans J, Joost O, Levy D . Heritability of longitudinal change in lung function. The Framingham study. Am J Respir Crit Care Med. 2001; 164(9):1655-9. DOI: 10.1164/ajrccm.164.9.2010122. View

Mannino D, Homa D, Akinbami L, Ford E, Redd S . Chronic obstructive pulmonary disease surveillance--United States, 1971-2000. MMWR Surveill Summ. 2002; 51(6):1-16. View

Cohen B, BALL Jr W, Brashears S, Diamond E, Kreiss P, Levy D . Risk factors in chronic obstructive pulmonary disease (COPD). Am J Epidemiol. 1977; 105(3):223-32. DOI: 10.1093/oxfordjournals.aje.a112378. View

Kueppers F, Miller R, Gordon H, HEPPER N, Offord K . Familial prevalence of chronic obstructive pulmonary disease in a matched pair study. Am J Med. 1977; 63(3):336-42. DOI: 10.1016/0002-9343(77)90270-4. View

10.

Silverman E, Chapman H, Drazen J, Weiss S, Rosner B, Campbell E . Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998; 157(6 Pt 1):1770-8. DOI: 10.1164/ajrccm.157.6.9706014. View

11.

Van Steen K, McQueen M, Herbert A, Raby B, Lyon H, DeMeo D . Genomic screening and replication using the same data set in family-based association testing. Nat Genet. 2005; 37(7):683-91. DOI: 10.1038/ng1582. View

12.

Hersh C, DeMeo D, Lazarus R, Celedon J, Raby B, Benditt J . Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006; 173(9):977-84. PMC: 2662917. DOI: 10.1164/rccm.200509-1452OC. View

13.

Hoffman E, Simon B, McLennan G . State of the Art. A structural and functional assessment of the lung via multidetector-row computed tomography: phenotyping chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006; 3(6):519-32. PMC: 2647643. DOI: 10.1513/pats.200603-086MS. View

14.

Lokke A, Lange P, Scharling H, Fabricius P, Vestbo J . Developing COPD: a 25 year follow up study of the general population. Thorax. 2006; 61(11):935-9. PMC: 2121175. DOI: 10.1136/thx.2006.062802. View

15.

DeMeo D, Hersh C, Hoffman E, Litonjua A, Lazarus R, Sparrow D . Genetic determinants of emphysema distribution in the national emphysema treatment trial. Am J Respir Crit Care Med. 2007; 176(1):42-8. PMC: 2049064. DOI: 10.1164/rccm.200612-1797OC. View

16.

Mannino D, Buist A . Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007; 370(9589):765-73. DOI: 10.1016/S0140-6736(07)61380-4. View

17.

Hersh C, DeMeo D, Reilly J, Silverman E . Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery. Respir Res. 2007; 8:59. PMC: 2048957. DOI: 10.1186/1465-9921-8-59. View

18.

Friedlander A, Lynch D, Dyar L, Bowler R . Phenotypes of chronic obstructive pulmonary disease. COPD. 2007; 4(4):355-84. DOI: 10.1080/15412550701629663. View