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. Lahousse; S.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

doi:10.1183/09031936.00001914

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	860-872
Number of pages	13
Journal	European Respiratory Journal
Volume	44
Issue number	4
DOIs	https://doi.org/10.1183/09031936.00001914
Publication status	Published - Oct 2014

Keywords

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

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10.1183/09031936.00001914

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

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title = "Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis",

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

author = "J. Smolonska and G.H. Koppelman and C. Wijmenga and J.M. Vonk and P. Zanen and M. Bruinenberg and I. Curjuric and M. Imboden and G.A. Thun and L. Franke and N.M. Probst-Hensch and P. N{\"u}rnberg and R.A. Riemersma and {van Schayck}, C.P. and D.W. Loth and G.G. Brusselle and B.H. Stricker and A. Hofman and A.G. Uitterlinden and L. Lahousse and S.J. London and L.R. Loehr and A. Manichaikul and R.G. Barr and K.M. Donohue and S.S. Rich and P. Pare and Y. Boss{\'e} and K. Hao and {van den Berge}, M. and H.J.M. Groen and J.W.J. Lammers and W. Mali and H.M. Boezen and D.S. Postma",

year = "2014",

month = oct,

doi = "10.1183/09031936.00001914",

language = "English",

volume = "44",

pages = "860--872",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "4",

}

Smolonska, J, Koppelman, GH, Wijmenga, C, Vonk, JM, Zanen, P, Bruinenberg, M, Curjuric, I, Imboden, M, Thun, GA, Franke, L, Probst-Hensch, NM, Nürnberg, P, Riemersma, RA, van Schayck, CP, Loth, DW, Brusselle, GG, Stricker, BH, Hofman, A, Uitterlinden, AG, Lahousse, L, London, SJ, Loehr, LR, Manichaikul, A, Barr, RG, Donohue, KM, Rich, SS, Pare, P, Bossé, Y, Hao, K, van den Berge, M, Groen, HJM, Lammers, JWJ, Mali, W, Boezen, HM & Postma, DS 2014, 'Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis', European Respiratory Journal, vol. 44, no. 4, pp. 860-872. https://doi.org/10.1183/09031936.00001914

TY - JOUR

T1 - Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis

AU - Smolonska, J.

AU - Koppelman, G.H.

AU - Wijmenga, C.

AU - Vonk, J.M.

AU - Zanen, P.

AU - Bruinenberg, M.

AU - Curjuric, I.

AU - Imboden, M.

AU - Thun, G.A.

AU - Franke, L.

AU - Probst-Hensch, N.M.

AU - Nürnberg, P.

AU - Riemersma, R.A.

AU - van Schayck, C.P.

AU - Loth, D.W.

AU - Brusselle, G.G.

AU - Stricker, B.H.

AU - Hofman, A.

AU - Uitterlinden, A.G.

AU - Lahousse, L.

AU - London, S.J.

AU - Loehr, L.R.

AU - Manichaikul, A.

AU - Barr, R.G.

AU - Donohue, K.M.

AU - Rich, S.S.

AU - Pare, P.

AU - Bossé, Y.

AU - Hao, K.

AU - van den Berge, M.

AU - Groen, H.J.M.

AU - Lammers, J.W.J.

AU - Mali, W.

AU - Boezen, H.M.

AU - Postma, D.S.

PY - 2014/10

Y1 - 2014/10

N2 - 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.

AB - 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.

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - LUNG-FUNCTION DECLINE

KW - SPIROMETRIC PHENOTYPES

KW - SUSCEPTIBILITY GENE

KW - LINKAGE ANALYSIS

KW - CANDIDATE GENE

KW - ADAM33 GENE

KW - FOLLOW-UP

KW - ASSOCIATION

KW - HYPERRESPONSIVENESS

U2 - 10.1183/09031936.00001914

DO - 10.1183/09031936.00001914

M3 - Article

C2 - 24993907

SN - 0903-1936

VL - 44

SP - 860

EP - 872

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

ER -