Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease

COPDGene and ECLIPSE Investigators

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population. Methods: We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis. Results: For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7). Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD. Trial registration: ClinicalTrials.gov NCT00608764, NCT00292552.

Original languageEnglish (US)
Article number113
JournalRespiratory Research
Volume15
Issue number1
DOIs
StatePublished - Sep 21 2014

Fingerprint

Chronic Bronchitis
Genetic Predisposition to Disease
Chronic Obstructive Pulmonary Disease
Spirometry
Genome
Genome-Wide Association Study
Norway
Cough
Single Nucleotide Polymorphism
Meta-Analysis
Cohort Studies
Chromosomes
Biomarkers
Smoking

Keywords

  • Chronic bronchitis
  • Chronic obstructive
  • Genome-wide association study
  • Pulmonary disease

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease. / COPDGene and ECLIPSE Investigators.

In: Respiratory Research, Vol. 15, No. 1, 113, 21.09.2014.

Research output: Contribution to journalArticle

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abstract = "Background: Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population. Methods: We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis. Results: For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7). Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD. Trial registration: ClinicalTrials.gov NCT00608764, NCT00292552.",
keywords = "Chronic bronchitis, Chronic obstructive, Genome-wide association study, Pulmonary disease",
author = "{COPDGene and ECLIPSE Investigators} and Lee, {Jin Hwa} and Cho, {Michael H.} and Hersh, {Craig P.} and McDonald, {Merry Lynn N} and Crapo, {James D.} and Bakke, {Per S.} and Amund Gulsvik and Comellas, {Alejandro P.} and Wendt, {Christine H.} and Lomas, {David A.} and Victor Kim and Silverman, {Edwin K.} and Regan, {Elizabeth A.} and Stephanie Bratschie and Rochelle Lantz and Sandra Melanson and Terri Beaty and Bowler, {Russell P.} and Curtis, {Jeffrey L.} and Douglas Everett and Han, {Mei Lan K} and Hokanson, {John E.} and {Rand Sutherland}, E. and Bleecker, {Eugene R.} and Crystal, {Ronald G.} and Hogg, {James C.} and Province, {Michael A.} and Rennard, {Stephen I.} and Thomas, {Duncan C.} and Thomas Croxton and Weiniu Gan and Lisa Postow and Walsh, {John W.} and Randel Plant and Delia Prieto and Daniel Cossette and Kelly, {Roxanne K.} and Andre Williams and Ruthie Knowles and Carla Wilson and Jennifer Black-Shinn and Gregory Kinney and Castaldi, {Peter J.} and Michael Cho and DeMeo, {Dawn L.} and Foreman, {Marilyn G.} and Anzueto, {Antonio R} and Adams, {Sandra G} and Mumbower, {Amy L} and Restrepo, {Carlos S}",
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T1 - Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease

AU - COPDGene and ECLIPSE Investigators

AU - Lee, Jin Hwa

AU - Cho, Michael H.

AU - Hersh, Craig P.

AU - McDonald, Merry Lynn N

AU - Crapo, James D.

AU - Bakke, Per S.

AU - Gulsvik, Amund

AU - Comellas, Alejandro P.

AU - Wendt, Christine H.

AU - Lomas, David A.

AU - Kim, Victor

AU - Silverman, Edwin K.

AU - Regan, Elizabeth A.

AU - Bratschie, Stephanie

AU - Lantz, Rochelle

AU - Melanson, Sandra

AU - Beaty, Terri

AU - Bowler, Russell P.

AU - Curtis, Jeffrey L.

AU - Everett, Douglas

AU - Han, Mei Lan K

AU - Hokanson, John E.

AU - Rand Sutherland, E.

AU - Bleecker, Eugene R.

AU - Crystal, Ronald G.

AU - Hogg, James C.

AU - Province, Michael A.

AU - Rennard, Stephen I.

AU - Thomas, Duncan C.

AU - Croxton, Thomas

AU - Gan, Weiniu

AU - Postow, Lisa

AU - Walsh, John W.

AU - Plant, Randel

AU - Prieto, Delia

AU - Cossette, Daniel

AU - Kelly, Roxanne K.

AU - Williams, Andre

AU - Knowles, Ruthie

AU - Wilson, Carla

AU - Black-Shinn, Jennifer

AU - Kinney, Gregory

AU - Castaldi, Peter J.

AU - Cho, Michael

AU - DeMeo, Dawn L.

AU - Foreman, Marilyn G.

AU - Anzueto, Antonio R

AU - Adams, Sandra G

AU - Mumbower, Amy L

AU - Restrepo, Carlos S

PY - 2014/9/21

Y1 - 2014/9/21

N2 - Background: Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population. Methods: We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis. Results: For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7). Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD. Trial registration: ClinicalTrials.gov NCT00608764, NCT00292552.

AB - Background: Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population. Methods: We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis. Results: For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7). Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD. Trial registration: ClinicalTrials.gov NCT00608764, NCT00292552.

KW - Chronic bronchitis

KW - Chronic obstructive

KW - Genome-wide association study

KW - Pulmonary disease

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DO - 10.1186/s12931-014-0113-2

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