Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease

Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints and COPDGene Investigators, Merry-Lynn N McDonald, Michael H Cho, Inga-Cecilie Sørheim, Sharon M Lutz, Peter J Castaldi, David A Lomas, Harvey O Coxson, Lisa D Edwards, William MacNee, Jørgen Vestbo, Julie C Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen I Rennard, Emiel F M Wouters, Per Bakke, Ruth Tal-SingerBruce E Miller, Amund Gulsvik, Richard Casaburi, J Michael Wells, Elizabeth A Regan, Barry J Make, John E Hokanson, Christoph Lange, James D Crapo, Terri H Beaty, Edwin K Silverman, Craig P Hersh

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)678-87
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number5
Publication statusPublished - Nov 2014

Keywords / Materials (for Non-textual outputs)

  • African Americans
  • Aged
  • Aged, 80 and over
  • Anoxia
  • Chromosomes, Human, Pair 15
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Oximetry
  • Oxygen
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive
  • Rest


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