biostudies-literatureHatzikotoulas KNCCDPHP CDC HHSRRD VANIAMS NIH HHS1217-1224https://www.ebi.ac.uk/biostudies/studies/S-EPMC12119359biostudies-literatureUnknown641(8065)Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes¹. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide². As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including transcriptome, proteome and epigenome profiles of primarNatureTranslational genomics of osteoarthritis in 1,962,069 individuals.PMC12119359U01 DP006266I01 RX002745P30 AR072580Lee MTMGabrielsen MKatsoula GKardia SLRLemmela SSugimoto SDaly MMartin NGUitterlinden AGLupton MKTragante VRosendaal FRNagami FTerao CPalotie AFinnGenPark YCBrunak SARGO ConsortiumPett JPCheung JTSGenes & Health Research TeamBaras AUchio YWinsvold BFaquih TTomizuka KBarysenka ATenghe AMMMook-Kanamori DOWu TTSingh JATiwari HKFei LHayward CTo KWeir DRCheung JPHuckins LMEaton CBUllum HTuerlings MMcCartney DYau MSGilly AHorn Svan Heel DAZeggini ELin KBabis GErikstrup CSchmidt COCarey DJHoijer JMinn AKKMillwood IYZhao WMichaelsson KLoef Mvan Meurs JBJShivakumar MThomas LSamartzis DHenkel CLotta LJohnson JSKloppenburg MArruda ALSmith JATroelsen ABanasik KRoberts MBAlexiadis GSoutham LCheah KSEKarjalainen JHatzikotoulas KNabika TDBDS Genomic ConsortiumGromov KFunayama TOstrowski SRWilkinson JMRegeneron Genetics CenterLietman SAFaul JDMeulenbelt Ide Pins AMIshijima MKang JHNelson AEPedersen OBRichman JTurman CMitchell BDFenstad AMZwart JAGolightly YMSilberstein MDThorleifsson GStefansson KTamiya GYue MDochtermann DIto SLukusa-Sawalena BJonsson HTsezou AHveem KKreitmaier PSorensen EMedland SEMillion Veteran ProgramChen ZChen LGZhou JJHailer NPFurnes ONChen SBarker TarcOGEN ConsortiumYamamoto MMola-Caminal MMagi RWalters RGGocho CLi LSong YQJones Mde Mutsert RIkegawa SKumahashi NHudjashov GSham PCIngvarsson TKraft PHochberg MCBittner NArbeeva LLerner RLee PHTeder-Laving MNarita ASuzuki KGabrielsen MEIsomura MKakehi SLiu XMulders RReimann EZengini EEstonian Biobank Research TeamStyrkarsdottir UTamura YMangino MWinsvold BSSmelser DTWeiss SLind PAMcDonald MLRyan KAMorris APBoer CGValdes AMHomuth GKasbohm ESrinivasasainagendra VSkou STDowsett JSakurai-Yageta MHansen TNguyen CTakuwa HHUNT All-In PainMcAlindon TEZhang YCampbell ARocco AGudbjartsson DFKuwata SStefansdottir LSkogholt AHTeichmann SAFerreira MARfalseTranslational genomics of osteoarthritis in 1,962,069 individuals.Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes¹. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide². As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including transcriptome, proteome and epigenome profiles of primar2025-01-01T00:00:00Z2025 May2026-06-03T07:40:51.315Z2026-04-26T03:09:49.032ZS-EPMC121193594020503610.1038/s41586-025-08771-z