title: Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.
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.
authors.affiliation: Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: Smolonska
authors.affiliation: GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.affiliation: Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.affiliation: Dept of Pulmonology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.affiliation: Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.affiliation: Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Curjuric
authors.affiliation: Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.affiliation: Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
authors.forename: Gian-Andri
authors.initials: GA
authors.lastname: Thun
authors.affiliation: Dept of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Riemersma
authors.affiliation: Dept of General Practice, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Constant P
authors.initials: CP
authors.lastname: van Schayck
authors.affiliation: Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Healthcare Inspectorate, The Hague, The Netherlands.
authors.forename: Daan W
authors.initials: DW
authors.lastname: Loth
authors.affiliation: Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium Dept of Respiratory Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Guy G
authors.initials: GG
authors.lastname: Brusselle
authors.affiliation: Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Healthcare Inspectorate, The Hague, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands Dept of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Dept of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: Lahousse
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA Dept of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: Dept of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: Dept of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Donohue
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Respiratory Division, Dept of Medicine, University of British Columbia James Hogg Research Centre, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Pare
authors.affiliation: Institut Universitaire De Cardiologie Et De Pneumologie De Québec, Dept of Molecular Medicine, Laval University, Québec, QC, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Dept of Genetics and Genomics Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: Dept of Pulmonology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jan-Willem J
authors.initials: JW
authors.lastname: Lammers
authors.affiliation: Dept of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Mali
authors.affiliation: Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: GRIAC Research Institute, Groningen University Medical Center, University of Groningen, Groningen, The Netherlands Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands d.s.postma@umcg.nl.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult