Choi, Seung HoanSeung HoanChoiJurgens, Sean JSean JJurgensXiao, LingLingXiaoHill, Matthew CMatthew CHillHaggerty, Christopher MChristopher MHaggertySveinbjörnsson, GarðarGarðarSveinbjörnssonMorrill, Valerie NValerie NMorrillMarston, Nicholas ANicholas AMarstonWeng, Lu-ChenLu-ChenWengPirruccello, James PJames PPirruccelloArnar, David ODavid OArnarGudbjartsson, Daniel FannarDaniel FannarGudbjartssonMantineo, HeleneHeleneMantineovon Falkenhausen, Aenne SAenne Svon FalkenhausenNatale, AndreaAndreaNataleTveit, ArnljotArnljotTveitGeelhoed, BastiaanBastiaanGeelhoedRoselli, CarolinaCarolinaRoselliVan Wagoner, David RDavid RVan WagonerDarbar, DawoodDawoodDarbarHaase, DoreenDoreenHaaseSoliman, Elsayed ZElsayed ZSolimanDavogustto, Giovanni EGiovanni EDavogusttoJun, GooGooJunCalkins, HughHughCalkinsAnderson, Jeffrey LJeffrey LAndersonBrody, Jennifer AJennifer ABrodyHalford, Jennifer LJennifer LHalfordBarnard, JohnJohnBarnardHokanson, John EJohn EHokansonSmith, Jonathan DJonathan DSmithBis, Joshua CJoshua CBisYoung, KendraKendraYoungJohnson, Linda S BLinda S BJohnsonRisch, LorenzLorenzRischGula, Lorne JLorne JGulaKwee, Lydia CoulterLydia CoulterKweeChaffin, Mark DMark DChaffinKühne, MichaelMichaelKühnePreuss, MichaelMichaelPreussGupta, NamrataNamrataGuptaNafissi, Navid ANavid ANafissiSmith, Nicholas LNicholas LSmithNilsson, Peter MPeter MNilssonvan der Harst, PimPimvan der HarstWells, Quinn SQuinn SWellsJudy, Renae LRenae LJudySchnabel, Renate BRenate BSchnabelJohnson, ReneeReneeJohnsonSmit, Roelof A JRoelof A JSmitGabriel, StaceyStaceyGabrielKnight, StaceyStaceyKnightFurukawa, TetsushiTetsushiFurukawaBlackwell, Thomas WThomas WBlackwellNauffal, VictorVictorNauffalWang, XinXinWangMin, Yuan-IYuan-IMinYoneda, Zachary TZachary TYonedaLaksman, Zachary W MZachary W MLaksmanBezzina, Connie RConnie RBezzinaAlonso, AlvaroAlvaroAlonsoPsaty, Bruce MBruce MPsatyAlbert, Christine MChristine MAlbertArking, Dan EDan EArkingRoden, Dan MDan MRodenChasman, Daniel IDaniel IChasmanRader, Daniel JDaniel JRaderConen, DavidDavidConenMcManus, David DDavid DMcManusFatkin, DianeDianeFatkinBenjamin, Emelia JEmelia JBenjaminBoerwinkle, EricEricBoerwinkleMarcus, Gregory MGregory MMarcusChristophersen, Ingrid EIngrid EChristophersenSmith, J GustavJ GustavSmithRoberts, Jason DJason DRobertsRaffield, Laura MLaura MRaffieldShoemaker, M BenjaminM BenjaminShoemakerCho, Michael HMichael HChoCutler, Michael JMichael JCutlerRienstra, MichielMichielRienstraChung, Mina KMina KChungS Olesen, MortenMortenS OlesenSinner, Moritz FMoritz FSinnerSotoodehnia, NonaNonaSotoodehniaKirchhof, PaulusPaulusKirchhofLoos, Ruth J FRuth J FLoosNazarian, SamanSamanNazarianMohanty, SanghamitraSanghamitraMohantyDamrauer, Scott MScott MDamrauerKaab, StefanStefanKaabHeckbert, Susan RSusan RHeckbertRedline, SusanSusanRedlineShah, Svati HSvati HShahTanaka, ToshihiroToshihiroTanakaEbana, YusukeYusukeEbanaHolm, HilmaHilmaHolmStefansson, KariKariStefanssonRuff, Christian TChristian TRuffSabatine, Marc SMarc SSabatineLunetta, Kathryn LKathryn LLunettaLubitz, Steven ASteven ALubitzEllinor, Patrick TPatrick TEllinorLEE-MING CHUANGet al.2025-04-082025-04-082025-03https://scholars.lib.ntu.edu.tw/handle/123456789/726265Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B in stem-cell-derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction. Our results highlight the contribution of rare coding and structural variants to AF, including genetic links between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia.enjournal article10.1038/s41588-025-02074-940050430