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Eur Respir J. 2014 Jul 3. pii: erj00019-2014. [Epub ahead of print]

Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.

Author information

  • 1Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands.
  • 2GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, University Medical Center, University of Groningen, Groningen, The Netherlands.
  • 3Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • 4Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands.
  • 5Dept of Pulmonology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • 6Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
  • 7Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • 8GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • 9Dept of General Practice, University of Maastricht, Maastricht, The Netherlands.
  • 10Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Healthcare Inspectorate, The Hague, The Netherlands.
  • 11Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Dept of Respiratory Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • 12Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Healthcare Inspectorate, The Hague, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands.
  • 13Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands.
  • 14Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands Dept of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • 15Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • 16Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC, USA.
  • 17University of North Carolina, Chapel Hill, NC, USA.
  • 18Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA Dept of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
  • 19Dept of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • 20Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • 21Respiratory Division, Dept of Medicine, University of British Columbia James Hogg Research Centre, St Paul's Hospital, Vancouver, BC, Canada.
  • 22Institut Universitaire De Cardiologie Et De Pneumologie De Québec, Dept of Molecular Medicine, Laval University, Québec, QC, Canada.
  • 23Dept of Genetics and Genomics Sciences, Mount Sinai School of Medicine, New York, NY, USA.
  • 24Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • 25Dept of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • 26GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands d.s.postma@umcg.nl.

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chr13q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) κβ pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p = 9.96×10-9). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression. Inflammatory processes differ in asthma and COPD and are mediated by NF-κβ, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution.

© ERS.

PMID:
24993907
[PubMed - as supplied by publisher]
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