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

Publication ,  Journal Article
Lee, JH; McDonald, M-LN; Cho, MH; Wan, ES; Castaldi, PJ; Hunninghake, GM; Marchetti, N; Lynch, DA; Crapo, JD; Lomas, DA; Coxson, HO; Bakke, PS ...
Published in: Respir Res
August 20, 2014

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.

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Published In

Respir Res

DOI

EISSN

1465-993X

Publication Date

August 20, 2014

Volume

15

Issue

1

Start / End Page

97

Location

England

Related Subject Headings

  • Total Lung Capacity
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Genome-Wide Association Study
  • Female
 

Citation

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Lee, J. H., McDonald, M.-L., Cho, M. H., Wan, E. S., Castaldi, P. J., Hunninghake, G. M., … COPDGene and ECLIPSE Investigators, . (2014). DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res, 15(1), 97. https://doi.org/10.1186/s12931-014-0097-y
Lee, Jin Hwa, Merry-Lynn N. McDonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, et al. “DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.Respir Res 15, no. 1 (August 20, 2014): 97. https://doi.org/10.1186/s12931-014-0097-y.
Lee JH, McDonald M-LN, Cho MH, Wan ES, Castaldi PJ, Hunninghake GM, et al. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res. 2014 Aug 20;15(1):97.
Lee, Jin Hwa, et al. “DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.Respir Res, vol. 15, no. 1, Aug. 2014, p. 97. Pubmed, doi:10.1186/s12931-014-0097-y.
Lee JH, McDonald M-LN, Cho MH, Wan ES, Castaldi PJ, Hunninghake GM, Marchetti N, Lynch DA, Crapo JD, Lomas DA, Coxson HO, Bakke PS, Silverman EK, Hersh CP, COPDGene and ECLIPSE Investigators. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res. 2014 Aug 20;15(1):97.

Published In

Respir Res

DOI

EISSN

1465-993X

Publication Date

August 20, 2014

Volume

15

Issue

1

Start / End Page

97

Location

England

Related Subject Headings

  • Total Lung Capacity
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Genome-Wide Association Study
  • Female