About the Authors

Akkelies E. Dijkstra

Affiliations University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands

Joanna Smolonska

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands

Maarten van den Berge

Affiliations University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands

Ciska Wijmenga

Affiliation University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands

Pieter Zanen

Affiliation University of Utrecht, University Medical Center Utrecht, Department of Pulmonology, Utrecht, the Netherlands

Marjan A. Luinge

Affiliation University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands

Mathieu Platteel

Affiliation University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands

Jan-Willem Lammers

Affiliation University of Utrecht, University Medical Center Utrecht, Department of Pulmonology, Utrecht, the Netherlands

Magnus Dahlback

Affiliation AstraZeneca, R&D Mölndal, Mölndal, Sweden

Kerrie Tosh

Affiliation AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom

Pieter S. Hiemstra

Affiliation Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands

Peter J. Sterk

Affiliation Department of Respiratory Medicine, University of Amsterdam, Amsterdam, the Netherlands

Avi Spira

Affiliation Department of Medicine, Section of Computational Biomedicine, Boston University Medical Center, Boston, Massachusetts, United States of America

Jorgen Vestbo

Affiliations Odense University Hospital, Department of Respiratory Medicine J, and University of Southern Denmark, Clinical Institute, Odense, Denmark, Respiratory and Allergy Research Group, Manchester Academic Health Sciences Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, United Kingdom

Borge G. Nordestgaard

Affiliations The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark

Marianne Benn

Affiliation Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark

Sune F. Nielsen

Affiliation The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark

Morten Dahl

Affiliation Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark

W. Monique Verschuren

Affiliation Center for Prevention and Health Services Research, National Institute for Public Health and the Environment, Bilthoven, the Netherlands

H. Susan J. Picavet

Affiliation Center for Prevention and Health Services Research, National Institute for Public Health and the Environment, Bilthoven, the Netherlands

Henriette A. Smit

Affiliation Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, the Netherlands

Michael Owsijewitsch

Affiliations Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany, Translational Lung Research Center (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany

Hans U. Kauczor

Affiliations Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany, Translational Lung Research Center (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany

Harry J. de Koning

Affiliation Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands

Eva Nizankowska-Mogilnicka

Affiliation Department of Respiratory Diseases, Jagiellonian University Medical College, Krakow, Poland

Filip Mejza

Affiliation Department of Respiratory Diseases, Jagiellonian University Medical College, Krakow, Poland

Pawel Nastalek

Affiliation Department of Respiratory Diseases, Jagiellonian University Medical College, Krakow, Poland

Cleo C. van Diemen

Affiliation University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands

Michael H. Cho

Affiliations Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America, Harvard Medical School, Boston, Massachusetts, United States of America

Edwin K. Silverman

Affiliations Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America, Harvard Medical School, Boston, Massachusetts, United States of America

James D. Crapo

Affiliation Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colorado, United States of America

Terri H. Beaty

Affiliation Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America

David A. Lomas

Affiliation Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

Per Bakke

Affiliation Department of Thoracic Medicine, Haukeland University, Hospital and Institute of Medicine, University of Bergen, Bergen, Norway

Amund Gulsvik

Affiliation Department of Thoracic Medicine, Haukeland University, Hospital and Institute of Medicine, University of Bergen, Bergen, Norway

Yohan Bossé

Affiliation Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec City, Canada

M. A. Obeidat

Affiliation Division of Respirology, Department of Medicine, James Hogg Research Centre, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada

Daan W. Loth

Affiliations Dept Epidemiology, Erasmus MC, Rotterdam, the Netherlands, The Netherlands Healthcare Inspectorate, The Hague, the Netherlands

Lies Lahousse

Affiliations Dept Epidemiology, Erasmus MC, Rotterdam, the Netherlands, Department of respiratory medicine, University Hospital Ghent, Ghent, Belgium

Fernando Rivadeneira

Affiliations Department of Internal medicine, Erasmus MC, Rotterdam, the Netherlands, Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands

Andre G. Uitterlinden

Affiliations Department of Internal medicine, Erasmus MC, Rotterdam, the Netherlands, Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands

Andre Hofman

Affiliations Dept Epidemiology, Erasmus MC, Rotterdam, the Netherlands, Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands

Bruno H. Stricker

Affiliations Dept Epidemiology, Erasmus MC, Rotterdam, the Netherlands, The Netherlands Healthcare Inspectorate, The Hague, the Netherlands

Guy G. Brusselle

Affiliations Dept Epidemiology, Erasmus MC, Rotterdam, the Netherlands, Department of respiratory medicine, University Hospital Ghent, Ghent, Belgium

Cornelia M. van Duijn

Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands

Uilke Brouwer

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands

Gerard H. Koppelman

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Beatrix Childrens' Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen, the Netherlands

Judith M. Vonk

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands

Martijn C. Nawijn

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands

Harry J. M. Groen

Affiliation University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands

Wim Timens

Affiliation University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands

H. Marike Boezen

Affiliations University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands

Dirkje S. Postma

d.s.postma@umcg.nl

Affiliations University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands, University of Groningen, University Medical Center Groningen, GRIAC research institute, Groningen, the Netherlands

the LifeLines Cohort study

Competing Interests

Firms occurring more frequently are coded as follows: A = AstraZeneca; B = Chiesi; C = Merck; D = Boehringer Ingelheim; E = GlaxoSmithKline; F = Nycomed; G = TEVA Pharma; H = Roche; I = Siemens; J = Pfizer. M. Dahlback and K. Tosh are employees of A. The University of Groningen: money for D. S. Postma regarding an unrestricted educational grant for research from A and B, an unrestricted grant for W. Timens from C, a grant from the Dutch Asthma Foundation for W. Timens, and grants for G. H. Koppelman and D. S. Postma from the BBMRI-NL, The Dutch Asthma Foundation and the Stichting Astma Bestrijding, and fees for consultancies of D. S. Postma by A, D, B, E, F, and G, and payment for lectures from A, B, and G and for consultancies of H. J. M. Groen by Eli Lilly, J and H. The University of Leiden: money for P. S. Hiemstra regarding an unrestricted educational grant for research from D, Galapagos. The University of Amsterdam: a public-private grant for P. S. Sterk by Innovative Medicine Initiative by European Union and European Federation of Pharmaceutical Industries and Associations. Boston University Medical Center holds patents. A. Spira: money for board membership, consultancy, and stock options from Allegro Diagnostics, Inc. Money for consultancy and for lectures was paid to J. Vestbo by E, F, B, Syntaxin, Bioxydyn, Novartis, A, and D. University Hospital of Heidelberg: money for expert testimony for H.U.Kauczor. H. U. Kauczor: money for board membership from I, for lectures from Bracco, I, D, and Bayer, and for development of educational presentations from I. The Jagiellonian University Medical College of Krakow: a Grant (Z/7PR/00010,201 379) for E. Nizankowska-Mogilnicka. E. Silverman: a grant for Harvard University from E. E. Silverman: consulting fee and support for travel to meetings for the study or other purposes (COPDGene and ECLIPSE) from E and the COPD foundation and money for consultancy and lectures from E, A and C. M. Cho: NIH/NHLBI grants (K12HL089990 and K08 HL097029) for Harvard University and money for consultancy from C. Erasmus Medical Center Rotterdam: a grant for H. de Koning from ZonMw, KWF, Kankerbestrijding, Stichting Centraal Fonds Reseves van Voormalig Vrijwillige Ziekenfondsverzekeringen; H provided a grant for the performance of proteomics research, and I provided 4-digital workstations for LungCare for the performance of 3Dmeasurements. Johns Hopkins Bloomberg School of Public Health in Baltimore: a NIH grant for J. Crapo. The National Jewish Health Center in Denver: a grant for T. Beaty from the National Institutes of Health and National Institute Heart, Lung & Blood Disease. T. Beaty: money for travel support by the COPD foundation. University of Cambridge: a grant for D. Lomas from E. D. Lomas: money for board membership, consultancy, lectures, and travel accommodations from E, Talecris/Grifols, and D. P. Bakke: money for lectures from E, A, and J. L. Lahousse: a travel award for the ATS (2012) and a short-term Research Fellowship for transport to Rotterdam. Part of the GLUCOLD study was supported by GlaxoSmithKline, the ECLIPSE study was partly funded by GSK, and the COPDGene study was partly funded by the COPD foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, and Sunovion. Data sampling for the Norway study was funded by GlaxoSmithKline. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. Patent nr. subjectdate 1US 2013/0023437Diagnostic for lung disorders using class prediction 2012-06-15 2US 2012/0322673Isolation of nucleic acid from mouth epithelial cells 2012-03-23 3US 2012/0190567Diagnostic and prognostic methods for lung disorders using gene expression profiles from nose epithelial cells 2011-12-12 4US 2011/0217717Diagnostic and prognostic methods for lung disorders using gene expression profiles from nose epithelial cells2010-11-05 5US 2011/0190150Isolation of nucleic acid from mouth epithelial cells 2010-09-17 6US 2012/0041686Diagnostic for lung disorders using class prediction 2010-08-26 7US 2010/0055689Multifactorial methods for detecting lung disorders2009-03-30 8US 2009/0311692Isolation of nucleic acid from mouth epithelial cells 2009-01-09 9US 2009/0186951Identification of novel pathways for drug development for lung disease 2008-09-19 10US 2009/0061454Diagnostic and prognostic methods for lung disorders using gene expression profiles from nose epithelial cells 2007-03-08 11 US 2010/0035244Diagnostic for lung disorders using class prediction2006-04-14 12US 2006/0154278Detection methods for disorders of the lung2005-12-06 13US 2007/0148650Isolation of nucleic acid from mouth epithelial cells2004-11-12.

Author Contributions

¶ Membership of the LifeLines Cohort study is provided in the Acknowledgments.

Conceived and designed the experiments: AED DSP HMB CW JS PZ HG JWL WT MCN MvdB. Performed the experiments: AED JS ML MCN UB MP. Analyzed the data: AED MvdB DL WT MHC MCN MP ML MB FM M. Obeidat. Contributed reagents/materials/analysis tools: ML MP JS M. Obeidat MvdB DL. Wrote the paper: AED DSP HMB CW JMV GHK PJS EKS MHC MCN. Acquisition of replication cohorts: M. Dahlback KT PSH PJS AS JV BGN M. Dahl WMV HSP HAS M. Owsijewitsch HUK HJK EN PN CCvD EKS JDC THB DAL PB AG YB LL FR AGU AH BHS GGB CMvD UB GHK SN.