Journal article
Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease
American journal of respiratory cell and molecular biology, Vol.51(5), pp.678-687
11/2014
DOI: 10.1165/rcmb.2014-0135OC
PMCID: PMC4224086
PMID: 24825563
Abstract
Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10−5) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10−8). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups.
Details
- Title: Subtitle
- Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease
- Creators
- Merry-Lynn N McDonald - Channing Division of Network Medicine, andMichael H Cho - Channing Division of Network Medicine, andInga-Cecilie Sørheim - Department of Clinical Science, University of Bergen, Bergen, NorwaySharon M Lutz - Colorado School of Public Health, Denver, ColoradoPeter J Castaldi - Channing Division of Network Medicine, andDavid A Lomas - Wolfson Institute for Biomedical Research, University College London, London, United KingdomHarvey O Coxson - University of British Columbia Department of Radiology and Vancouver General Hospital, Vancouver, British Columbia, CanadaLisa D Edwards - GlaxoSmithKline, Research Triangle Park, North CarolinaWilliam MacNee - Department of Respiratory and Environmental Medicine, University of Edinburgh, Edinburgh, ScotlandJørgen Vestbo - Department of Respiratory Medicine, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester, United KingdomJulie C Yates - GlaxoSmithKline, Research Triangle Park, North CarolinaPeter M. A Calverley - Department of Pulmonary and Rehabilitation Medicine, University of Liverpool, Liverpool, United KingdomBartolome Celli - Department of Clinical Science, University of Bergen, Bergen, NorwayCourtney Crim - GlaxoSmithKline, Research Triangle Park, North CarolinaStephen I Rennard - Department of Medicine, University of Nebraska Medical Center, Omaha, NebraskaEmiel F. M Wouters - Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The NetherlandsPer Bakke - Department of Clinical Science, University of Bergen, Bergen, NorwayRuth Tal-Singer - GlaxoSmithKline, King of Prussia, PennsylvaniaBruce E Miller - GlaxoSmithKline, King of Prussia, PennsylvaniaAmund Gulsvik - Department of Clinical Science, University of Bergen, Bergen, NorwayRichard Casaburi - Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor–University of California Los Angeles Medical Center, Torrance, CaliforniaJ. Michael Wells - Divison of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AlabamaElizabeth A Regan - Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, Denver, ColoradoBarry J Make - Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, Denver, ColoradoJohn E Hokanson - Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, ColoradoChristoph Lange - Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; andJames D Crapo - Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, Denver, ColoradoTerri H Beaty - Johns Hopkins School of Public Health, Baltimore, MarylandEdwin K Silverman - Channing Division of Network Medicine, andCraig P Hersh - Channing Division of Network Medicine, andEvaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints and COPDGene Investigators
- Contributors
- Alejandro Comellas (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.51(5), pp.678-687
- DOI
- 10.1165/rcmb.2014-0135OC
- PMID
- 24825563
- PMCID
- PMC4224086
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984094648302771
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