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

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 Nürnberg, Peter and Riemersma, Roland A. and van Schayck, Constant P. and Loth, Daan W. and Brusselle, Guy G. and Stricker, Bruno H. and Hofman, Albert and Uitterlinden, André 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 Bossé, Yohan and Hao, Ke and van den Berge, Maarten and Groen, Harry J. M. and Lammers, Jan-Willem J. and Mali, Willem and Boezen, H. Marike and Postma, Dirkje S.. (2014) Common genes underlying asthma and COPD? : Genome-wide analysis on the Dutch hypothesis. The European respiratory journal, 44 (4). pp. 860-872.

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Official URL: http://edoc.unibas.ch/dok/A6308540

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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 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Munksgaard
ISSN:0903-1936
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 May 2018 09:37
Deposited On:07 Nov 2014 08:28

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