Journal article
DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease
Respiratory research, Vol.15(1), pp.97-97
2014
DOI: 10.1186/s12931-014-0097-y
PMCID: PMC4169636
PMID: 25134640
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 × 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.
Details
- Title: Subtitle
- DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease
- Creators
- Jin Hwa Lee - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USAMerry-Lynn N McDonald - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USAMichael H Cho - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USAEmily S Wan - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USAPeter J Castaldi - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USAGary M Hunninghake - Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Boston, MA USANathaniel Marchetti - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, PA USADavid A Lynch - National Jewish Health, Denver, CO USAJames D Crapo - National Jewish Health, Denver, CO USADavid A Lomas - Wolfson Institute for Biomedical Research, University College London, London, UKHarvey O Coxson - Department of Radiology, University of British Columbia, Vancouver, CanadaPer S Bakke - Department of Clinical Science, University of Bergen, Bergen, NorwayEdwin K Silverman - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USACraig P Hersh - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115 USACOPDGene & ECLIPSE Investigators
- Contributors
- Alejandro Comellas (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.15(1), pp.97-97
- DOI
- 10.1186/s12931-014-0097-y
- PMID
- 25134640
- PMCID
- PMC4169636
- NLM abbreviation
- Respir Res
- ISSN
- 1465-9921
- eISSN
- 1465-993X
- Publisher
- BioMed Central
- Language
- English
- Date published
- 2014
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984094482402771
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