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

(2014) EUROPEAN RESPIRATORY JOURNAL. 44(4). p.860-872
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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.
Keywords
LUNG-FUNCTION DECLINE, SUSCEPTIBILITY GENE, SPIROMETRIC PHENOTYPES, LINKAGE ANALYSIS, OBSTRUCTIVE PULMONARY-DISEASE, CANDIDATE GENE, ADAM33 GENE, FOLLOW-UP, ASSOCIATION, HYPERRESPONSIVENESS

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Chicago
Smolonska, Joanna, Gerard H Koppelman, Cisca Wijmenga, Judith M Vonk, Pieter Zanen, Marcel Bruinenberg, Ivan Curjuric, et al. 2014. “Common Genes Underlying Asthma and COPD? : Genome-wide Analysis on the Dutch Hypothesis.” European Respiratory Journal 44 (4): 860–872.
APA
Smolonska, J., Koppelman, G. H., Wijmenga, C., Vonk, J. M., Zanen, P., Bruinenberg, M., Curjuric, I., et al. (2014). Common genes underlying asthma and COPD? : genome-wide analysis on the Dutch hypothesis. EUROPEAN RESPIRATORY JOURNAL, 44(4), 860–872.
Vancouver
1.
Smolonska J, Koppelman GH, Wijmenga C, Vonk JM, Zanen P, Bruinenberg M, et al. Common genes underlying asthma and COPD? : genome-wide analysis on the Dutch hypothesis. EUROPEAN RESPIRATORY JOURNAL. 2014;44(4):860–72.
MLA
Smolonska, Joanna, Gerard H Koppelman, Cisca Wijmenga, et al. “Common Genes Underlying Asthma and COPD? : Genome-wide Analysis on the Dutch Hypothesis.” EUROPEAN RESPIRATORY JOURNAL 44.4 (2014): 860–872. Print.
@article{5776548,
  abstract     = {Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ({\textacutedbl}Dutch hypothesis{\textacutedbl}). 
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.},
  author       = {Smolonska, Joanna and Koppelman, Gerard H and Wijmenga, Cisca and Vonk, Judith M and Zanen, Pieter and Bruinenberg, Marcel and Curjuric, Ivan and Imboden, Medea and Thun, Gian-Andri and Franke, Lude and Probst-Hensch, Nicole M and N{\"u}rnberg, Peter and Riemersma, Roland A and van Schayck, Constant P and Loth, Daan W and Brusselle, Guy and Stricker, Bruno H and Hofman, Albert and Uitterlinden, Andr{\'e} G and Lahousse, Lies and London, Stephanie J and Loehr, Laura R and Manichaikul, Ani and Barr, R Graham and Donohue, Kathleen M and Rich, Stephen S and Pare, Peter and Boss{\'e}, Yohan and Hao, Ke and van den Berge, Maarten and Groen, Harry JM and Lammers, Jan-Willem J and Mali, Willem and Boezen, H Marike and Postma, Dirkje S},
  issn         = {0903-1936},
  journal      = {EUROPEAN RESPIRATORY JOURNAL},
  language     = {eng},
  number       = {4},
  pages        = {860--872},
  title        = {Common genes underlying asthma and COPD? : genome-wide analysis on the Dutch hypothesis},
  url          = {http://dx.doi.org/10.1183/09031936.00001914},
  volume       = {44},
  year         = {2014},
}

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