DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

the COPDGene and ECLIPSE Investigators

doi:10.1186/s12931-014-0097-y

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

the COPDGene and ECLIPSE Investigators

Brigham and Women's Hospital
Ewha Womans University School of Medicine
Temple University
University of Alabama at Birmingham
National Jewish Health
University College London
University of British Columbia
University of Bergen
Haukeland University Hospital
Columbia University
Temple University
University of Minnesota Twin Cities
Johns Hopkins University
NHLBI
COPD Foundation
Candidate Genotyping Core
Baylor College of Medicine
University of Michigan, Ann Arbor
Duke University Medical Center
Reliant Medical Group
HealthPartners Research Foundation
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Methodist DeBakey Heart and Vascular Center
Morehouse School of Medicine
University of California San Diego
University of Iowa
University of Pittsburgh
University of Texas Health Science Center at San Antonio
GlaxoSmithKline, USA

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

24 Citations (Scopus)

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) <0.7 and FEV₁ < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10^-8).Conclusions: In COPD, TLC_CT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Original language	English
Article number	97
Journal	Respiratory Research
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12931-014-0097-y
Publication status	Published - 20 Aug 2014
Externally published	Yes

Keywords

Chronic obstructive
DNAH5
Genome-wide association analysis
Hyperinflation
Pulmonary disease
Total lung capacity

Access to Document

10.1186/s12931-014-0097-y

Cite this

@article{12bef0fd2fb04daf80a63b781bc62716,

title = "DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease",

abstract = "Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80\% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 {\texttimes} 10-8).Conclusions: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.",

keywords = "Chronic obstructive, DNAH5, Genome-wide association analysis, Hyperinflation, Pulmonary disease, Total lung capacity",

author = "\{the COPDGene and ECLIPSE Investigators\} and Lee, \{Jin H.\} and McDonald, \{Merry Lynn N.\} and Cho, \{Michael H.\} and Wan, \{Emily S.\} and Castaldi, \{Peter J.\} and Hunninghake, \{Gary M.\} and Nathaniel Marchetti and Lynch, \{David A.\} and Crapo, \{James D.\} and Lomas, \{David A.\} and Coxson, \{Harvey O.\} and Bakke, \{Per S.\} and Silverman, \{Edwin K.\} and Hersh, \{Craig P.\} and Stephanie Bratschie and Rochelle Lantz and Sandra Melanson and Lori Stepp and Russell Bowler and Curtis, \{Jeffrey L.\} and Han, \{Mei Lan\} and Hokanson, \{John E.\} and Make, \{Barry J.\} and Sutherland, \{E. Rand\} 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 Douglas Everett and Andre Williams and Ruthie Knowles and Carla Wilson and John Hokanson and Jennifer Black-Shinn and Gregory Kinney and Michael Cho and Dawn DeMeo and Foreman, \{Marilyn G.\} and Hansel, \{Nadia N.\} and Hardin, \{Megan E.\} and Jacqueline Hetmanski and Nan Laird and Christoph Lange and Lutz, \{Sharon M.\} and Manuel Mattheisen and Parker, \{Margaret M.\} and Regan, \{Elizabeth A.\} and Stephanie Santorico and Jin Zhou and Qaisi, \{Mustafa Al\} and Jaleh Akhavan and Cox, \{Christian W.\} and Deanna Cusick and Dy, \{Jennifer G.\} and Shoshana Ginsburg and Hoffman, \{Eric A.\} and Judy, \{Philip F.\} and Alex Kluiber and Alexander McKenzie and Newell, \{John D.\} and Reilly, \{John J.\} and James Ross and Estepar, \{Raul San Jose\} and Schroeder, \{Joyce D.\} and Jered Sieren and Arkadiusz Sitek and Douglas Stinson and Jordan Zach and Robert Jensen and Terri Beaty and R. Stacey and Homayoon Farzadegan and Samantha Bragan and Stacey Cayetano and Jeffrey Curtis and Ella Kazerooni and Nicola Hanania and Philip Alapat and Venkata Bandi and Kalpalatha Guntupalli and Elizabeth Guy and Antara Mallampalli and Charles Trinh and Mustafa Atik and Hasan Al-Azzawi and Linda Fahr and Frigini, \{L. Alexander\} and David Katz and Jose Freytes and John Newell",

note = "Publisher Copyright: {\textcopyright} 2014 Lee et al.; licensee BioMed Central Ltd.",

year = "2014",

month = aug,

day = "20",

doi = "10.1186/s12931-014-0097-y",

language = "English",

volume = "15",

journal = "Respiratory Research",

issn = "1465-9921",

publisher = "BioMed Central Ltd",

number = "1",

}

TY - JOUR

T1 - DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

AU - the COPDGene and ECLIPSE Investigators

AU - Lee, Jin H.

AU - McDonald, Merry Lynn N.

AU - Cho, Michael H.

AU - Wan, Emily S.

AU - Castaldi, Peter J.

AU - Hunninghake, Gary M.

AU - Marchetti, Nathaniel

AU - Lynch, David A.

AU - Crapo, James D.

AU - Lomas, David A.

AU - Coxson, Harvey O.

AU - Bakke, Per S.

AU - Silverman, Edwin K.

AU - Hersh, Craig P.

AU - Bratschie, Stephanie

AU - Lantz, Rochelle

AU - Melanson, Sandra

AU - Stepp, Lori

AU - Bowler, Russell

AU - Curtis, Jeffrey L.

AU - Han, Mei Lan

AU - Hokanson, John E.

AU - Make, Barry J.

AU - Sutherland, E. Rand

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 - Everett, Douglas

AU - Williams, Andre

AU - Knowles, Ruthie

AU - Wilson, Carla

AU - Hokanson, John

AU - Black-Shinn, Jennifer

AU - Kinney, Gregory

AU - Cho, Michael

AU - DeMeo, Dawn

AU - Foreman, Marilyn G.

AU - Hansel, Nadia N.

AU - Hardin, Megan E.

AU - Hetmanski, Jacqueline

AU - Laird, Nan

AU - Lange, Christoph

AU - Lutz, Sharon M.

AU - Mattheisen, Manuel

AU - Parker, Margaret M.

AU - Regan, Elizabeth A.

AU - Santorico, Stephanie

AU - Zhou, Jin

AU - Qaisi, Mustafa Al

AU - Akhavan, Jaleh

AU - Cox, Christian W.

AU - Cusick, Deanna

AU - Dy, Jennifer G.

AU - Ginsburg, Shoshana

AU - Hoffman, Eric A.

AU - Judy, Philip F.

AU - Kluiber, Alex

AU - McKenzie, Alexander

AU - Newell, John D.

AU - Reilly, John J.

AU - Ross, James

AU - Estepar, Raul San Jose

AU - Schroeder, Joyce D.

AU - Sieren, Jered

AU - Sitek, Arkadiusz

AU - Stinson, Douglas

AU - Zach, Jordan

AU - Jensen, Robert

AU - Beaty, Terri

AU - Stacey, R.

AU - Farzadegan, Homayoon

AU - Bragan, Samantha

AU - Cayetano, Stacey

AU - Curtis, Jeffrey

AU - Kazerooni, Ella

AU - Hanania, Nicola

AU - Alapat, Philip

AU - Bandi, Venkata

AU - Guntupalli, Kalpalatha

AU - Guy, Elizabeth

AU - Mallampalli, Antara

AU - Trinh, Charles

AU - Atik, Mustafa

AU - Al-Azzawi, Hasan

AU - Fahr, Linda

AU - Frigini, L. Alexander

AU - Katz, David

AU - Freytes, Jose

AU - Newell, John

PY - 2014/8/20

Y1 - 2014/8/20

N2 - Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10-8).Conclusions: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

AB - Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10-8).Conclusions: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

KW - Chronic obstructive

KW - DNAH5

KW - Genome-wide association analysis

KW - Hyperinflation

KW - Pulmonary disease

KW - Total lung capacity

UR - https://www.scopus.com/pages/publications/84908157737

U2 - 10.1186/s12931-014-0097-y

DO - 10.1186/s12931-014-0097-y

M3 - Article

C2 - 25134640

AN - SCOPUS:84908157737

SN - 1465-9921

VL - 15

JO - Respiratory Research

JF - Respiratory Research

IS - 1

M1 - 97

ER -

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Abstract

Keywords

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