Nick ShrineAnna L. GuyattA. Mesut ErzurumluogluVictoria E. JacksonBrian D. HobbsCarl A. MelbourneChiara BatiniKatherine A. FawcettKijoung SongPhuwanat SakornsakolpatXingnan LiRuth BoxallNicola F. ReeveMa’en ObeidatJing Hua ZhaoMatthias WielscherStefan WeissKatherine A. KentistouJames P. CookBenjamin B. SunJian ZhouJennie HuiStefan KarraschMedea ImbodenSarah E. HarrisJonathan MartenStefan EnrothShona M. KerrIda SurakkaVeronique VitartTerho LehtimäkiRichard J. AllenPer S. BakkeTerri H. BeatyEugene R. BleeckerYohan BosséCorry Anke BrandsmaZhengming ChenJames D. CrapoJohn DaneshDawn L. DeMeoFrank DudbridgeRalf EwertChristian GiegerAmund GulsvikAnna L. HansellKe HaoJoshua D. HoffmanJohn E. HokansonGeorg HomuthPeter K. JoshiPhilippe JoubertClaudia LangenbergXuan LiLiming LiKuang LinLars LindNicholas LocantoreJian’an LuanAnubha MahajanJoseph C. MaranvilleAlison MurrayDavid C. NickleRichard PackerMargaret M. ParkerMegan L. PayntonDavid J. PorteousDmitry ProkopenkoDandi QiaoRajesh RawalHeiko RunzIan SayersDon D. SinBlair H. SmithMaría Soler ArtigasDavid SparrowRuth Tal-SingerPaul R.H.J. TimmersMaarten Van den BergeJohn C. WhittakerPrescott G. WoodruffLaura M. Yerges-ArmstrongOlga G. TroyanskayaOlli T. RaitakariMika KähönenOzren PolašekUlf GyllenstenIgor RudanIan J. DearyNicole M. Probst-HenschHolger SchulzAlan L. JamesJames F. WilsonBeate StubbeEleftheria ZegginiMarjo Riitta JarvelinNick WarehamEdwin K. SilvermanCaroline HaywardAndrew P. MorrisVA Boston Healthcare SystemSimons FoundationCentro de Investigación Biomédica En Red de Salud MentalNational Institute for Health and WelfareNational Jewish HealthWellcome Trust Centre for Human GeneticsGlaxoSmithKline, USAInstitut universitaire de cardiologie et de pneumologie de Québec - Université LavalUniversity of LeicesterUniversité LavalUniversity of Western AustraliaUniversity of CambridgeUniversitetet i BergenLudwig-Maximilians-Universität MünchenUniversity of Colorado at Denver Anschutz Medical CampusWalter and Eliza Hall Institute of Medical ResearchUniversity of EdinburghUniversity of OxfordUniversity of MelbourneSir Charles Gairdner HospitalTurun Yliopistollinen KeskussairaalaSchool of Clinical MedicineHelmholtz Center Munich German Research Center for Environmental HealthUniversity of California, San FranciscoUniversity of Dundee College of Medicine, Dentistry and NursingUniversitat BaselSwiss Tropical and Public Health Institute (Swiss TPH)Universitat Autònoma de BarcelonaSt Mary's Hospital LondonUniversity of LiverpoolGlaxoSmithKline plc.Brunel University LondonAddenbrooke's HospitalBrigham and Women's HospitalOulu University HospitalImperial College LondonUniversity of NottinghamIcahn School of Medicine at Mount SinaiOulun YliopistoEdinburgh Medical School, Medical Research Council Human Genetics UnitHospital Universitari Vall d'HebronFaculty of Medicine, Siriraj Hospital, Mahidol UniversityTampereen YliopistoUniversity of Aberdeen School of MedicineThe University of British ColumbiaUniversity of ArizonaUniversity of Western Australia Faculty of Medicine and DentistryUniversity Hospital of TampereMerck & Co., Inc.Sveučilište u SplituTurun yliopistoBoston University School of MedicineJohns Hopkins Bloomberg School of Public HealthUniversity of Groningen, University Medical Center GroningenWellcome Sanger InstitutePeking University Health Science CenterUppsala UniversitetPrinceton UniversityHelsingin YliopistoWestfälische Wilhelms-Universität MünsterGossamer BioMember of the German Center for Lung Research (DZL)University Medicine Greifswald2020-01-272020-01-272019-03-01Nature Genetics. Vol.51, No.3 (2019), 481-49315461718106140362-s2.0-85062074587https://repository.li.mahidol.ac.th/handle/20.500.14594/50248© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function–associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/s41588-018-0321-7