Year: 2014
Type: article
Study design: Observational Study
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.
Source: European Respiratory Journal
Authors: Joanna Smolonska, Gerard H. Koppelman, Cisca Wijmenga, Judith M. Vonk, Pieter Zanen, Marcel Bruinenberg, Ivan Curjuric, Medea Imboden, Gian-Andri Thun, Lude Franke, Nicole M. Probst-Hensch, Peter Nürnberg, Roland A. Riemersma, Constant P. van Schayck, Daan W. Loth, Guy G. Brusselle, Bruno H. Stricker, Albert Hofman, André G. Uitterlinden, Lies Lahousse, Stephanie J. London, Laura R. Loehr, Ani Manichaikul, R. Graham Barr, Kathleen M. Donohue, Stephen S. Rich, Peter Pare, Yohan Bossé, Ke Hao, Maarten van den Berge, Harry J.M. Groen, Jan-Willem J. Lammers, Willem Mali, H. Marike Boezen, Dirkje S. Postma
Institutions: University Medical Center Groningen, University of Groningen, University Medical Center Utrecht, Swiss Tropical and Public Health Institute, University of Basel, University of Cologne, Maastricht University, Dutch Health Care Inspectorate, Erasmus MC, Ghent University Hospital, Netherlands Consortium for Healthy Ageing, National Institutes of Health, National Institute of Environmental Health Sciences, University of North Carolina at Chapel Hill, University of Virginia, Columbia University, University of British Columbia, St. Paul's Hospital, Centre for Heart Lung Innovation, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Heart and Stroke Foundation of Canada, Université Laval, Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen, National Institutes of Health, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences
OpenAlex ID: W1974540015