Smolonska, Joanna, Koppelman, Gerard H., Wijmenga, Cisca ORCID: 0000-0002-5635-1614, Vonk, Judith M., Zanen, Pieter, Bruinenberg, Marcel, Curjuric, Ivan, Imboden, Medea, Thun, Gian-Andri, Franke, Lude ORCID: 0000-0002-5159-8802, Probst-Hensch, Nicole M., Nuernberg, Peter, Riemersma, Roland A., van Schayck, Constant P., Loth, Daan W., Brusselle, Guy G., Stricker, Bruno H., Hofman, Albert, Uitterlinden, Andre G., Lahousse, Lies ORCID: 0000-0002-3494-4363, London, Stephanie J., Loehr, Laura R., Manichaikul, Ani, Barr, R. Graham, Donohue, Kathleen M., Rich, Stephen S., Pare, Peter, Bosse, Yohan, Hao, Ke, van den Berge, Maarten ORCID: 0000-0002-9336-7340, Groen, Harry J. M., Lammers, Jan-Willem J., Mali, Willem, Boezen, H. Marike and Postma, Dirkje S. (2014). Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis. Eur. Resp. J., 44 (4). S. 860 - 873. SHEFFIELD: EUROPEAN RESPIRATORY SOC JOURNALS LTD. ISSN 1399-3003

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Smolonska, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koppelman, Gerard H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wijmenga, CiscaUNSPECIFIEDorcid.org/0000-0002-5635-1614UNSPECIFIED
Vonk, Judith M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zanen, PieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruinenberg, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curjuric, IvanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imboden, MedeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thun, Gian-AndriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, LudeUNSPECIFIEDorcid.org/0000-0002-5159-8802UNSPECIFIED
Probst-Hensch, Nicole M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemersma, Roland A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Schayck, Constant P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loth, Daan W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brusselle, Guy G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stricker, Bruno H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofman, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uitterlinden, Andre G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lahousse, LiesUNSPECIFIEDorcid.org/0000-0002-3494-4363UNSPECIFIED
London, Stephanie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loehr, Laura R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manichaikul, AniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barr, R. GrahamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Donohue, Kathleen M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rich, Stephen S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pare, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosse, YohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hao, KeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Berge, MaartenUNSPECIFIEDorcid.org/0000-0002-9336-7340UNSPECIFIED
Groen, Harry J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammers, Jan-Willem J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mali, WillemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boezen, H. MarikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Postma, Dirkje S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-427990
DOI: 10.1183/09031936.00001914
Journal or Publication Title: Eur. Resp. J.
Volume: 44
Number: 4
Page Range: S. 860 - 873
Date: 2014
Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD
Place of Publication: SHEFFIELD
ISSN: 1399-3003
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION DECLINE; SPIROMETRIC PHENOTYPES; SUSCEPTIBILITY GENE; LINKAGE ANALYSIS; CANDIDATE GENE; ADAM33 GENE; ASSOCIATION; POLYMORPHISMS; BURDENMultiple languages
Respiratory SystemMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42799

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