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

J. Smolonska, G.H. Koppelman, C. Wijmenga, J.M. Vonk, P. Zanen, M. Bruinenberg, I. Curjuric, M. Imboden, G.A. Thun, L. Franke, N.M. Probst-Hensch, P. Nürnberg, R.A. Riemersma, C.P. van Schayck, D.W. Loth, G.G. Brusselle, B.H. Stricker, A. Hofman, A.G. Uitterlinden, L. LahousseS.J. London, L.R. Loehr, A. Manichaikul, R.G. Barr, K.M. Donohue, S.S. Rich, P. Pare, Y. Bossé, K. Hao, M. van den Berge, H.J.M. Groen, J.W.J. Lammers, W. Mali, H.M. Boezen, D.S. Postma

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23 Citations (Scopus)

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 chrl3q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) kappa beta pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96 x 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-kappa beta, 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.

Original languageEnglish
Pages (from-to)860-872
Number of pages13
JournalEuropean Respiratory Journal
Volume44
Issue number4
DOIs
Publication statusPublished - Oct 2014

Keywords

  • OBSTRUCTIVE PULMONARY-DISEASE
  • LUNG-FUNCTION DECLINE
  • SPIROMETRIC PHENOTYPES
  • SUSCEPTIBILITY GENE
  • LINKAGE ANALYSIS
  • CANDIDATE GENE
  • ADAM33 GENE
  • FOLLOW-UP
  • ASSOCIATION
  • HYPERRESPONSIVENESS

Cite this

Smolonska, J., Koppelman, G. H., Wijmenga, C., Vonk, J. M., Zanen, P., Bruinenberg, M., Curjuric, I., Imboden, M., Thun, G. A., Franke, L., Probst-Hensch, N. M., Nürnberg, P., Riemersma, R. A., van Schayck, C. P., Loth, D. W., Brusselle, G. G., Stricker, B. H., Hofman, A., Uitterlinden, A. G., ... Postma, D. S. (2014). Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis. European Respiratory Journal, 44(4), 860-872. https://doi.org/10.1183/09031936.00001914