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Common genes underlying asthma and COPD? : Genome-wide analysis on the Dutch hypothesis
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 2733603
Author(s) Smolonska, Joanna; Koppelman, Gerard H.; Wijmenga, Cisca; Vonk, Judith M.; Zanen, Pieter; Bruinenberg, Marcel; Curjuric, Ivan; Imboden, Medea; Thun, Gian-Andri; Franke, Lude; Probst-Hensch, Nicole M.; Nürnberg, Peter; Riemersma, Roland A.; van Schayck, Constant P.; Loth, Daan W.; Brusselle, Guy G.; Stricker, Bruno H.; Hofman, Albert; Uitterlinden, André G.; Lahousse, Lies; London, Stephanie J.; Loehr, Laura R.; Manichaikul, Ani; Barr, R. Graham; Donohue, Kathleen M.; Rich, Stephen S.; Pare, Peter; Bossé, Yohan; Hao, Ke; van den Berge, Maarten; Groen, Harry J. M.; Lammers, Jan-Willem J.; Mali, Willem; Boezen, H. Marike; Postma, Dirkje S.
Author(s) at UniBasel Probst Hensch, Nicole
Year 2014
Title Common genes underlying asthma and COPD? : Genome-wide analysis on the Dutch hypothesis
Journal The European respiratory journal
Volume 44
Number 4
Pages / Article-Number 860-72
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.
Publisher Munksgaard
ISSN/ISBN 0903-1936
Full Text on edoc No
Digital Object Identifier DOI 10.1183/09031936.00001914
PubMed ID
ISI-Number WOS:000342543700010
Document type (ISI) Journal Article

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