Suzuki, KenKenSuzukiHatzikotoulas, KonstantinosKonstantinosHatzikotoulasSoutham, LorraineLorraineSouthamTaylor, Henry JHenry JTaylorYin, XianyongXianyongYinLorenz, Kim MKim MLorenzMandla, RaviRaviMandlaHuerta-Chagoya, AliciaAliciaHuerta-ChagoyaMelloni, Giorgio E MGiorgio E MMelloniKanoni, StavroulaStavroulaKanoniRayner, Nigel WNigel WRaynerBocher, OzvanOzvanBocherArruda, Ana LuizaAna LuizaArrudaSonehara, KyutoKyutoSoneharaNamba, ShinichiShinichiNambaLee, Simon S KSimon S KLeePreuss, Michael HMichael HPreussPetty, Lauren ELauren EPettySchroeder, PhilipPhilipSchroederVanderwerff, BrettBrettVanderwerffKals, MartMartKalsBragg, FionaFionaBraggLin, KuangKuangLinGuo, XiuqingXiuqingGuoZhang, WeihuaWeihuaZhangYao, JieJieYaoKim, Young JinYoung JinKimGraff, MariaelisaMariaelisaGraffTakeuchi, FumihikoFumihikoTakeuchiNano, JanaJanaNanoLamri, AmelAmelLamriNakatochi, MasahiroMasahiroNakatochiMoon, SanghoonSanghoonMoonScott, Robert ARobert AScottCook, James PJames PCookLee, Jung-JinJung-JinLeePan, IanIanPanTaliun, DanielDanielTaliunParra, Esteban JEsteban JParraChai, Jin-FangJin-FangChaiBielak, Lawrence FLawrence FBielakTabara, YasuharuYasuharuTabaraHai, YangYangHaiThorleifsson, GudmarGudmarThorleifssonGrarup, NielsNielsGrarupSofer, TamarTamarSoferWuttke, MatthiasMatthiasWuttkeSarnowski, ChloéChloéSarnowskiGieger, ChristianChristianGiegerNousome, DarrylDarrylNousomeTrompet, StellaStellaTrompetKwak, Soo-HeonSoo-HeonKwakLong, JirongJirongLongSun, MengMengSunTong, LinLinTongChen, Wei-MinWei-MinChenNongmaithem, Suraj SSuraj SNongmaithemNoordam, RaymondRaymondNoordamLim, Victor J YVictor J YLimTam, Claudia H TClaudia H TTamJoo, Yoonjung YoonieYoonjung YoonieJooChen, Chien-HsiunChien-HsiunChenRaffield, Laura MLaura MRaffieldPrins, Bram PeterBram PeterPrinsNicolas, AudeAudeNicolasYanek, Lisa RLisa RYanekChen, GuanjieGuanjieChenBrody, Jennifer AJennifer ABrodyKabagambe, EdmondEdmondKabagambeAn, PingPingAnXiang, Anny HAnny HXiangChoi, Hyeok SunHyeok SunChoiCade, Brian EBrian ECadeTan, JingyiJingyiTanBroadaway, K AlaineK AlaineBroadawayWilliamson, AliceAliceWilliamsonKamali, ZohaZohaKamaliCui, JinruiJinruiCuiThangam, ManonanthiniManonanthiniThangamAdair, Linda SLinda SAdairAdeyemo, AdebowaleAdebowaleAdeyemoAguilar-Salinas, Carlos ACarlos AAguilar-SalinasAhluwalia, Tarunveer STarunveer SAhluwaliaAnand, Sonia SSonia SAnandBertoni, AlainAlainBertoniBork-Jensen, JetteJetteBork-JensenBrandslund, IvanIvanBrandslundBuchanan, Thomas AThomas ABuchananBurant, Charles FCharles FBurantButterworth, Adam SAdam SButterworthCanouil, MickaëlMickaëlCanouilChan, Juliana C NJuliana C NChanChang, Li-ChingLi-ChingChangChee, Miao-LiMiao-LiCheeChen, JiJiChenChen, Shyh-HueiShyh-HueiChenChen, Yuan-TsongYuan-TsongChenChen, ZhengmingZhengmingChenLEE-MING CHUANGCushman, MaryMaryCushmanDanesh, JohnJohnDaneshDas, Swapan KSwapan KDasde Silva, H JanakaH Janakade SilvaDedoussis, GeorgeGeorgeDedoussisDimitrov, LatchezarLatchezarDimitrovDoumatey, Ayo PAyo PDoumateyDu, ShufaShufaDuDuan, QingQingDuanEckardt, Kai-UweKai-UweEckardtEmery, Leslie SLeslie SEmeryEvans, Daniel SDaniel SEvansEvans, Michele KMichele KEvansFischer, KristaKristaFischerFloyd, James SJames SFloydFord, IanIanFordFranco, Oscar HOscar HFrancoFrayling, Timothy MTimothy MFraylingFreedman, Barry IBarry IFreedmanGenter, PaulinePaulineGenterGerstein, Hertzel CHertzel CGersteinGiedraitis, VilmantasVilmantasGiedraitisGonzález-Villalpando, ClicerioClicerioGonzález-VillalpandoGonzález-Villalpando, Maria ElenaMaria ElenaGonzález-VillalpandoGordon-Larsen, PennyPennyGordon-LarsenGross, MyronMyronGrossGuare, Lindsay ALindsay AGuareHackinger, SophieSophieHackingerHakaste, LiisaLiisaHakasteHan, SoheeSoheeHanHattersley, Andrew TAndrew THattersleyHerder, ChristianChristianHerderHorikoshi, MomokoMomokoHorikoshiHoward, Annie-GreenAnnie-GreenHowardHsueh, WillaWillaHsuehHuang, MengnaMengnaHuangHuang, WeiWeiHuangHung, Yi-JenYi-JenHungHwang, Mi YeongMi YeongHwangHwu, Chii-MinChii-MinHwuIchihara, SahokoSahokoIchiharaIkram, Mohammad ArfanMohammad ArfanIkramIngelsson, MartinMartinIngelssonIslam, Md TariqulMd TariqulIslamIsono, MasatoMasatoIsonoJang, Hye-MiHye-MiJangJasmine, FarzanaFarzanaJasmineJiang, GuozhiGuozhiJiangJonas, Jost BJost BJonasJørgensen, TorbenTorbenJørgensenKamanu, Frederick KFrederick KKamanuKandeel, Fouad RFouad RKandeelKasturiratne, AnuradhaniAnuradhaniKasturiratneKatsuya, TomohiroTomohiroKatsuyaKaur, VarinderpalVarinderpalKaurKawaguchi, TakahisaTakahisaKawaguchiKeaton, Jacob MJacob MKeatonKho, Abel NAbel NKhoKhor, Chiea-ChuenChiea-ChuenKhorKibriya, Muhammad GMuhammad GKibriyaKim, Duk-HwanDuk-HwanKimKronenberg, FlorianFlorianKronenbergKuusisto, JohannaJohannaKuusistoLäll, KristiKristiLällLange, Leslie ALeslie ALangeLee, Kyung MinKyung MinLeeLee, Myung-ShikMyung-ShikLeeLee, Nanette RNanette RLeeLeong, AaronAaronLeongLi, LimingLimingLiLi, YunYunLiLi-Gao, RuifangRuifangLi-GaoLigthart, SymenSymenLigthartLindgren, Cecilia MCecilia MLindgrenLinneberg, AllanAllanLinnebergLiu, Ching-TiChing-TiLiuLiu, JianjunJianjunLiuLocke, Adam EAdam ELockeLouie, TinTinLouieLuan, Jian'anJian'anLuanLuk, Andrea OAndrea OLukLuo, XiXiLuoLv, JunJunLvLynch, Julie AJulie ALynchLyssenko, ValeriyaValeriyaLyssenkoMaeda, ShiroShiroMaedaMamakou, VasilikiVasilikiMamakouMansuri, Sohail RafikSohail RafikMansuriMatsuda, KoichiKoichiMatsudaMeitinger, ThomasThomasMeitingerMelander, OlleOlleMelanderMetspalu, AndresAndresMetspaluMo, HuanHuanMoMorris, Andrew DAndrew DMorrisMoura, Filipe AFilipe AMouraNadler, Jerry LJerry LNadlerNalls, Michael AMichael ANallsNayak, UmaUmaNayakNtalla, IoannaIoannaNtallaOkada, YukinoriYukinoriOkadaOrozco, LorenaLorenaOrozcoPatel, Sanjay RSanjay RPatelPatil, SnehalSnehalPatilPei, PeiPeiPeiPereira, Mark AMark APereiraPeters, AnnetteAnnettePetersPirie, Fraser JFraser JPiriePolikowsky, Hannah GHannah GPolikowskyPorneala, BiancaBiancaPornealaPrasad, GauriGauriPrasadRasmussen-Torvik, Laura JLaura JRasmussen-TorvikReiner, Alexander PAlexander PReinerRoden, MichaelMichaelRodenRohde, RebeccaRebeccaRohdeRoll, KatherynKatherynRollSabanayagam, CharumathiCharumathiSabanayagamSandow, KevinKevinSandowSankareswaran, AlaguAlaguSankareswaranSattar, NaveedNaveedSattarSchönherr, SebastianSebastianSchönherrShahriar, MohammadMohammadShahriarShen, BotongBotongShenShi, JinxiuJinxiuShiShin, Dong MunDong MunShinShojima, NobuhiroNobuhiroShojimaSmith, Jennifer AJennifer ASmithSo, Wing YeeWing YeeSoStančáková, AlenaAlenaStančákováSteinthorsdottir, ValgerdurValgerdurSteinthorsdottirStilp, Adrienne MAdrienne MStilpStrauch, KonstantinKonstantinStrauchTaylor, Kent DKent DTaylorThorand, BarbaraBarbaraThorandThorsteinsdottir, UnnurUnnurThorsteinsdottirTomlinson, BrianBrianTomlinsonTran, Tam CTam CTranTsai, Fuu-JenFuu-JenTsaiTuomilehto, JaakkoJaakkoTuomilehtoTusie-Luna, TeresaTeresaTusie-LunaUdler, Miriam SMiriam SUdlerValladares-Salgado, AdanAdanValladares-Salgadovan Dam, Rob MRob Mvan Damvan Klinken, Jan BJan Bvan KlinkenVarma, RohitRohitVarmaWacher-Rodarte, NielsNielsWacher-RodarteWheeler, EleanorEleanorWheelerWickremasinghe, Ananda RAnanda RWickremasinghevan Dijk, Ko WillemsKo Willemsvan DijkWitte, Daniel RDaniel RWitteYajnik, Chittaranjan SChittaranjan SYajnikYamamoto, KenKenYamamotoYamamoto, KenichiKenichiYamamotoYoon, KyungheonKyungheonYoonYu, CanqingCanqingYuYuan, Jian-MinJian-MinYuanYusuf, SalimSalimYusufZawistowski, MatthewMatthewZawistowskiZhang, LiangLiangZhangZheng, WeiWeiZhengRaffel, Leslie JLeslie JRaffelIgase, MichiyaMichiyaIgaseIpp, EliEliIppRedline, SusanSusanRedlineCho, Yoon ShinYoon ShinChoLind, LarsLarsLindProvince, Michael AMichael AProvinceFornage, MyriamMyriamFornageHanis, Craig LCraig LHanisIngelsson, ErikErikIngelssonZonderman, Alan BAlan BZondermanPsaty, Bruce MBruce MPsatyWang, Ya-XingYa-XingWangRotimi, Charles NCharles NRotimiBecker, Diane MDiane MBeckerMatsuda, FumihikoFumihikoMatsudaLiu, YongmeiYongmeiLiuYokota, MitsuhiroMitsuhiroYokotaKardia, Sharon L RSharon L RKardiaPeyser, Patricia APatricia APeyserPankow, James SJames SPankowEngert, James CJames CEngertBonnefond, AmélieAmélieBonnefondFroguel, PhilippePhilippeFroguelWilson, James GJames GWilsonSheu, Wayne H HWayne H HSheuWu, Jer-YuarnJer-YuarnWuHayes, M GeoffreyM GeoffreyHayesMa, Ronald C WRonald C WMaWong, Tien-YinTien-YinWongMook-Kanamori, Dennis ODennis OMook-KanamoriTuomi, TiinamaijaTiinamaijaTuomiChandak, Giriraj RGiriraj RChandakCollins, Francis SFrancis SCollinsBharadwaj, DwaipayanDwaipayanBharadwajParé, GuillaumeGuillaumeParéSale, Michèle MMichèle MSaleAhsan, HabibulHabibulAhsanMotala, Ayesha AAyesha AMotalaShu, Xiao-OuXiao-OuShuPark, Kyong-SooKyong-SooParkJukema, J WouterJ WouterJukemaCruz, MiguelMiguelCruzChen, Yii-Der IdaYii-Der IdaChenRich, Stephen SStephen SRichMcKean-Cowdin, RobertaRobertaMcKean-CowdinGrallert, HaraldHaraldGrallertCheng, Ching-YuChing-YuChengGhanbari, MohsenMohsenGhanbariTai, E-ShyongE-ShyongTaiDupuis, JoseeJoseeDupuisKato, NorihiroNorihiroKatoLaakso, MarkkuMarkkuLaaksoKöttgen, AnnaAnnaKöttgenKoh, Woon-PuayWoon-PuayKohBowden, Donald WDonald WBowdenPalmer, Colin N AColin N APalmerKooner, Jaspal SJaspal SKoonerKooperberg, CharlesCharlesKooperbergLiu, SiminSiminLiuNorth, Kari EKari ENorthSaleheen, DanishDanishSaleheenHansen, TorbenTorbenHansenPedersen, OlufOlufPedersenWareham, Nicholas JNicholas JWarehamLee, JuyoungJuyoungLeeKim, Bong-JoBong-JoKimMillwood, Iona YIona YMillwoodWalters, Robin GRobin GWaltersStefansson, KariKariStefanssonAhlqvist, EmmaEmmaAhlqvistGoodarzi, Mark OMark OGoodarziMohlke, Karen LKaren LMohlkeLangenberg, ClaudiaClaudiaLangenbergHaiman, Christopher AChristopher AHaimanLoos, Ruth J FRuth J FLoosFlorez, Jose CJose CFlorezRader, Daniel JDaniel JRaderRitchie, Marylyn DMarylyn DRitchieZöllner, SebastianSebastianZöllnerMägi, ReedikReedikMägiMarston, Nicholas ANicholas AMarstonRuff, Christian TChristian TRuffvan Heel, David ADavid Avan HeelFiner, SarahSarahFinerDenny, Joshua CJoshua CDennyYamauchi, ToshimasaToshimasaYamauchiKadowaki, TakashiTakashiKadowakiChambers, John CJohn CChambersNg, Maggie C YMaggie C YNgSim, XuelingXuelingSimBelow, Jennifer EJennifer EBelowTsao, Philip SPhilip STsaoChang, Kyong-MiKyong-MiChangMcCarthy, Mark IMark IMcCarthyMeigs, James BJames BMeigsMahajan, AnubhaAnubhaMahajanSpracklen, Cassandra NCassandra NSpracklenMercader, Josep MJosep MMercaderBoehnke, MichaelMichaelBoehnkeRotter, Jerome IJerome IRotterVujkovic, MarijanaMarijanaVujkovicVoight, Benjamin FBenjamin FVoightMorris, Andrew PAndrew PMorrisZeggini, EleftheriaEleftheriaZeggini2024-04-262024-04-262024-030028-08361476-4687https://scholars.lib.ntu.edu.tw/handle/123456789/642056Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.enjournal article10.1038/s41586-024-07019-6383742562-s2.0-85186615049https://api.elsevier.com/content/abstract/scopus_id/85186615049