biostudies-literatureSakornsakolpat PMedical Research CouncilNHLBI NIH HHSNational Institute for Health Research (NIHR)Wellcome TrustBiotechnology and Biological Sciences Research Council494-505https://www.ebi.ac.uk/biostudies/studies/S-EPMC6546635biostudies-literatureUnknown51(3)Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10^-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. Nature geneticsGenetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.PMC6546635K01 HL129039R01 HL111024MR/S003762/1R01 HL084323R01 HL089856MR/N024842/1R01 HL113264U01 HL089856G0700704MC_QA137853P01 HL105339MR/N011317/118050841805065MC_PC_17228R01 HL137927MC_UU_00007/10K08 HL136928BB/F019394/1G1000861G0700704BMC_PC_12010R01 HL097163MR/K026992/1P01 HL132825T32 HL007085NF-SI-0617-10096R01 HL135142202849/Z/16/ZR33 HL120770Bakke PSchwartz DAWain LVBatini CCook JPCrystal RKarrasch SBelinsky SAde Bruijne MWanner ALuan JZhao JHKim WJOh YMHarris SEMahajan ADeary IJShort AEnroth SSchulz HLaitinen TWareham NHayward CGuyatt ALWashko GWauters ESparrow DHall IPNewell JDQiao DRaitakari OTHui JBartz TMGharib SAFingerlin TELitonjua AACelli BBoezen HMMacNee WLynch DWouters EFMZeggini ELee MKSliwinski PTobin MDKalsheker NCastaldi PJKerr SMvan Ginneken BLamontagne MBarr RGSilverman EKPostma DSVonk JMGarcia-Aymerich JKauczor HUBeaty THProbst-Hensch NMRawal RWyss ABSurakka IWielscher MYoung RPMeyers DAReeve NFSmith BHLee SDBrightling CKim DKZhou XSverzellati NGhosh SLambrechts DHersh CPRegan ELomas DARennard SIHansel NPare PDZeigler-Heitbrock LBrusselle GGTesfaigzi YO'Connor GTGevenois PHokanson JERich SSWilson JFObeidat MLatourelle JCBakerly NMurray AProkopenko DNordestgaard BGMarten JShrine NJoshi PKSeo JBGieger CKentistou KAEwert RImboden MMorrow JDTal-Singer RKahonen MLoth DWPorteous DJCho MHJames ALJarvelin MRLutz SMLi XGyllensten UBowler RInternational COPD Genetics ConsortiumSakornsakolpat PGulsvik AManichaikul ADirksen AAgusti ADeMeo DLJackson VEDy JLahousse LCoxson HOPolasek OSpiroMeta ConsortiumHobbs BDAnderson WForeman MGietema HCrapo JDVan Beek EJRLind LVogelmeier CFYim JJWeiss SMorris APMcDonald MLLehtimaki THoffman Ede Jong PRudan IHomuth GBleecker ERTer Riet Gde Jong KStrachan DPVitart VLondon SJLangenberg CVestbo JPistolesi MTimmers PRHJBals RStoel BBarnes KCStubbe BPuhan MBosse YfalseGenetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10^-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. 2019-01-01T00:00:00Z2019 Mar2026-05-07T18:08:44.88Z2026-04-07T23:04:21.275ZS-EPMC65466353080456110.1038/s41588-018-0342-2