RT Journal Article
SR Electronic
T1 Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 860
OP 872
DO 10.1183/09031936.00001914
VO 44
IS 4
A1 Joanna Smolonska
A1 Gerard H. Koppelman
A1 Cisca Wijmenga
A1 Judith M. Vonk
A1 Pieter Zanen
A1 Marcel Bruinenberg
A1 Ivan Curjuric
A1 Medea Imboden
A1 Gian-Andri Thun
A1 Lude Franke
A1 Nicole M. Probst-Hensch
A1 Peter Nürnberg
A1 Roland A. Riemersma
A1 Constant P. van Schayck
A1 Daan W. Loth
A1 Guy G. Brusselle
A1 Bruno H. Stricker
A1 Albert Hofman
A1 André G. Uitterlinden
A1 Lies Lahousse
A1 Stephanie J. London
A1 Laura R. Loehr
A1 Ani Manichaikul
A1 R. Graham Barr
A1 Kathleen M. Donohue
A1 Stephen S. Rich
A1 Peter Pare
A1 Yohan Bossé
A1 Ke Hao
A1 Maarten van den Berge
A1 Harry J.M. Groen
A1 Jan-Willem J. Lammers
A1 Willem Mali
A1 H. Marike Boezen
A1 Dirkje S. Postma
YR 2014
UL http://erj.ersjournals.com/content/44/4/860.abstract
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 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. This article provides suggestive evidence, but not firm evidence that there is overlap in genetics of asthma and COPD http://ow.ly/we9yE