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Item A saturated map of common genetic variants associated with human height(Nature Publishing Group, 2022) Vedantam, S.; Marouli, E.; Sidorenko, J.; Bartell, E.; Sakaue, S.; Graff, M.; Eliasen, A.U.; Jiang, Y.; Raghavan, S.; Miao, J.; Arias, J.D.; Graham, S.E.; Mukamel, R.E.; Spracklen, C.N.; Yin, X.; Chen, S.H.; Ferreira, T.; Highland, H.H.; Ji, Y.; Karaderi. T,; Lin, K.; Lüll, K.; Malden, D.E.; Medina-Gomez, C.; Machado, M.; Moore, A.; Rüeger, S.; Sim. X,; Vrieze, S.; Ahluwalia, T.S.; Akiyama, M.; Allison, M.A.; Alvarez, M.; Andersen, M.K.; Ani, A.; Appadurai, V.; Arbeeva, L.; Bhaskar, S.; Bielak, L.F.; Bollepalli, S.; Bonnycastle, L.L.; Bork-Jensen, J.; Bradfield, J.P.; Bradford, Y.; Braund, P.S.; Brody, J.A.; Burgdorf, K.S.; Cade, B.E.; Cai, H.; Cai, Q.; Campbell, A.; Cañadas-Garre, M.; Catamo, E.; Chai, J.F.; Chai, X.; Chang, L.C.; Chen, C.H.; Chesi, A.; Choi, S.H.; Chung, R.H.; Cocca, M.; Concas, M.P.; Couture, C.; Cuellar-Partida, G.; Danning, R.; Daw, E.W.; Degenhard, F.; Delgado, G.E.; Delitala, A.; Demirkan, A.; Deng, X.; Devineni, P.; Dietl, A.; Dimitriou, M.; Dimitrov, L.; Dorajoo, R.; Ekici, A.B.; Engmann, J.E.; Fairhurst-Hunter, Z.; Farmaki, A.E.; Faul, J.D.; Fernandez-Lopez, J.C.; Forer, L.; Francescatto, M.; Freitag-Wolf, S.; Fuchsberger, C.; Galesloot, T.E.; Gao, Y.; Gao, Z.; Geller, F.; Giannakopoulou, O.; Giulianini,F.; Gjesing, A.P.; Goel, A.; Gordon, S.D.; Gorski, M.; Grove, J.; Guo, X.; Gustafsson, S.; Haessler, J.; Hansen, T.F.; Havulinna, A.S.; Haworth, S.J.; He, J.; Heard-Costa, N.; Hebbar, P.; Hindy, G.; Ho, Y.A.; Hofer, E.; Holliday, E.; Horn, K.; Hornsby, W.E.; Hottenga, J.J.; Huang, H.; Huang, J.; Huerta-Chagoya, A.; Huffman, J.E.; Hung, Y.J.; Huo, S.; Hwang, M.Y.; Ha, H.; Ikeda, D.D.; Isono, M.; Jackson, A.U.; Jäger, S.; Jansen, I.E.; Johansson, I.; Jonas, J.B.; Jonsson, A.; Jørgensen, T.; Kalafati, I.P.; Kanai, M.; Kanoni, S.; Kårhus, L.L.; Kasturiratne, A.; Katsuya, T.; Kawaguchi, T.; Kember, R.L.; Kentistou, K.A.; Kim, H.N.; Kim, Y.J.; Kleber, M.E.; Knol, M.J.; Kurbasic, A.; Lauzon, M.; Le, P.; Lea, R.; Lee, J.Y.; Leonard, H.L.; Li, S.A.; Li, X.; Li, X.; Liang, J.; Lin, H.; Lin, S.Y.; Liu, J.; Liu, X.; Lo, K.S.; Long, J.; Lores-Motta, L.; Luan, J.; Lyssenko, V.; Lyytikäinen, L.P.; Mahajan, A.; Mamakou, V.; Mangino, M.; Manichaikul, A.; Marten, J.,; Mattheisen, M.; Mavarani, L.; McDaid, A.F.; Meidtner, K.; Melendez, T.L.; Mercader, J.M.; Milaneschi, Y.; Miller, J.E.; Millwood, I.Y.; Mishra, P.P.; Mitchell, R.E.; Møllehave, L.T.; Morgan, A.; Mucha, S.; Munz, M.; Nakatochi, M.; Nelson, C.P.; Nethander, M.; Nho, C.W.; Nielsen, A.A.; Nolte, I.M.; Nongmaithem, S.S.; Noordam, R.; Ntalla, I.; Nutile, T.; Pandit, A.; Christofidou, P.; Pärna, K.; Pauper, M.; Petersen, E.R.B.; Petersen, L.V.; Pitkänen, N.; Polašek, O.; Poveda, A.; Preuss, M.H.; Pyarajan, S.; Raffield, L.M.; Rakugi, H.; Ramirez, J.; Rasheed, A.; Raven, D.; Rayner, N.W.; Riveros, C.; Rohde, R.; Ruggiero, D.; Ruotsalainen, S.E.; Ryan, K.A.; Sabater-Lleal, M.; Saxena, R.; Scholz, M.; Sendamarai, A.; Shen, B.; Shi, J.; Shin, J.H.; Sidore, C.; Sitlani, C.M.; Slieker, R.C.; Smit, R.A.J.; Smith, A.V.; Smith, J.A.; Smyth, L.J.; Southam, L.; Steinthorsdottir, V.; Sun, L.; Takeuchi, F.; Tallapragada, D.S.P.; Taylor, K.D.; Tayo, B.O.; Tcheandjieu, C.; Terzikhan, N.; Tesolin, P.; Teumer, A.; Theusch, E.; Thompson, D.J.; Thorleifsson, G.; Timmers, P.R.H.J.; Trompet, S.; Turman, C.; Vaccargiu, S.; van der Laan, S.W.; van der Most, P.J.; van Klinken, J.B.; van Setten, J.; Verma, S.S.; Verweij, N.; Veturi, Y.; Wang, C.A.; Wang, C.; Wang, L.; Wang, Z.; Warren, H.R.; Bin Wei, W.; Wickremasinghe, A.R.; Wielscher, M.; Wiggins, K.L.; Winsvold, B.S.; Wong, A.; Wu, Y.; Wuttke, M.; Xia, R.; Xie, T.; Yamamoto, K.; Yang, J.; Yao, J.; Young, H.; Yousri, N.A.; Yu, L.; Zeng, L.; Zhang, W.; Zhang, X.; Zhao, J.H.; Zhao. W.; Zhou, W.; Zimmermann, M.E.; Zoledziewska, M.; Adair, L.S.; Adams, H.H.H.; Aguilar-Salinas, C.A.; Al-Mulla, F.; Arnett, D.K.; Arnett, D.K.; Asselbergs, F.W.; Åsvold, B.O.; Attia, J.; Banas, B.; Bandinelli, S.; Bennett D.A.; Bergler, T.; Bharadwaj, D.; Biino, G.; Bisgaard, H.; Boerwinkle, E.; Böger, C.A.; Bønnelykke, K.; Boomsma, D.I.; Børglum, A.D.; Borja, J.B.; Bouchard, C.; Bowden, D.W.; Brandslund, I.; Brumpton, B.; Buring, J.E.; Caulfield, M.J.; Chambers, J.C.; Chandak, G.R.; Chanock, S.J.; Chaturvedi, N.; Chen, Y.I.; Chen, Z.; Cheng, C.Y.; Christophersen, I.E.; Ciullo, M.; Cole, J.W.; Collins, F.S.; Cooper, R.S.; Cruz, M.; Cucca, F.; Cupples, L.A.; Cutler, M.J.; Damrauer, S.M.; Dantoft, T.M.; de Borst, G.J.; de Groot, L.C.P.G.M.; de Jager, P.L.; de Kleijn, D.P.V.; de Silva, H.J.; Dedoussis, G.V.; den Hollander, A.I.; Du, S.; Easton, D.F.; Elders, P.J.M.; Eliassen, A.H.; Ellinor, P.T.; Elmståhl, S.; Erdmann, J.; Evans, M.K.; Fatkin, D.; Feenstra, B.; Feitosa, M.F.; Ferrucci, L.; Ford, I.; Fornage, M.; Franke, A.; Franks, P.W.; Freedman, B.I.; Gasparini, P.; Gieger, C.; Girotto, G.; Goddard, M.E.; Golightly, Y.M.; Gonzalez-Villalpando. C.; Gordon-Larsen, P.; Grallert, H.; Grant, S.F.A.; Grarup, N.; Griffiths, L.; Gudnason, V.; Haiman, C.; Hakonarson, H.; Hansen, T.; Hartman, C.A.; Hattersley, A.T.; Hayward, C.; Heckbert, S.R.; Heng, C.K.; Hengstenberg, C.; Hewitt, A.W.; Hishigaki, H.; Hoyng, C.B.; Huang, P.L.; Huang, W.; Hunt, S.C.; Hveem, K.; Hyppönen, E.; Iacono, W.G.; Ichihara, S.; Ikram, M.A.; Isasi, C.R.; Jackson, R.D.; Jarvelin, M.R.; Jin, Z.B.; Jöckel, K.H.; Joshi, P.K.; Jousilahti, P.; Jukema, J.W.; Kähönen, M.; Kamatani, Y.; Kang, K.D.; Kaprio, J.; Kardia, S.L.R.; Karpe, F.; Kato, N.; Kee, F.; Kessler, T.; Khera, A.V.; Khor, C.C.; Kiemeney, L.A.L.M.; Kim, B.J.; Kim, E.K.; Kim, H.L.; Kirchhof, P.; Kivimaki, M.; Koh, W.P.; Koistinen, H.A.; Kolovou, G.D.; Kooner, J.S.; Kooperberg, C.; Köttgen, A.; Kovacs, P.; Kraaijeveld, A.; Kraft, P.; Krauss, R.M.; Kumari, M.; Kutalik, Z.; Laakso, M.; Lange, L.A.; Langenberg, C.; Launer, L.J.; Le Marchand, L.; Lee, H.; Lee, N.R.; Lehtimäki, T.; Li, H.; Li, L.; Lieb, W.; Lin, X.; Lind, L.; Linneberg, A.; Liu, C.T.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Magnusson, P.K.E.; Marcus, G.M.; Vidal, P.M.; Martin, N.G.; Martin, N.G.; Lieb, W.; Lin, X.; Lind, L.; Linneberg, A.; Liu, C.T.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Mägi, R.; Magnusson, P.K.E.; Marcus, G.M.; Vidal, P.M.; Martin, N.G.; März, W.; Matsuda, F.; McGarrah, R.W.; McGue, M.; McKnight, A.J.; Medland, S.E.; Mellström, D.; Metspalu, A.; Mitchell, B.D.; Mitchell, P.; Mook-Kanamori, D.O.; Morris, A.D.; Mucci, L.A.; Munroe, P.B.; Nalls, M.A.; Nazarian, S.; Nelson, A.E.; Neville, M.J.; Newton-Cheh, C.; Nielsen, C.S.; Nöthen, M.M.; Ohlsson, C.; Oldehinkel, A.J.; Oldehinkel, A.J.; Orozco, L.; Pahkala, K.; Pajukanta, P.; Palmer, C.N.A.; Parra, E.J.; Pattaro, C.; Pedersen, O.; Pennell, C.E.; Penninx, B.W.J.H.; Perusse, L.; Peters, A.; Peyser, P.A.; Porteous, D.J.; Posthuma, D.; Power, C.; Pramstaller, P.P.; Province, M.A.; Qi, Q.; Qu, J.; Rader, D.J.; Raitakari, O.T.; Ralhan, S.; Rallidis, L.S.; Rao, D.C.; Redline, S.; Reilly, D.F.; Reiner, A.P.; Rhee, S.Y.; Ridker, P.M.; Rienstra, M.; Ripatti, S.; Ritchie, M.D.; Roden, D.M.; Rosendaal, F.R.; Rotter, J.I.; Rudan, I.; Rutters, F.; Sabanayagam, C.; Saleheen, D.; Salomaa, V.; Samani, N.J.; Sanghera, D.K.; Sattar, N.; Schmidt, B.; Schmidt, H.; Schmidt, R.; Schulze, M.B.; Schunkert, H.; Scott, L.J.; Scott, R.J.; Sever, P.; Shiroma, E.J.; Shoemaker, M.B.; Shu, X.O.; Simonsick, E.M.; Sims, M.; Singh, J.R.; Singleton, A.B.; Sinner, M.F.; Smith, J.G.; Snieder, H.; Spector, T.D.; Stampfer, M.J.; Stark, K.J.; Strachan, D.P.; 't Hart, L.M.; Tabara, Y.; Tang, H.; Tardif, J.C.; Thanaraj, T.A.; Timpson, N.J.; Tönjes, A.; Tremblay, A.; Tuomi, T.; Tuomilehto, J.; Tusié-Luna, M.T.; Uitterlinden, A.G.; van Dam, R.M.; van der Harst, P.; Van der Velde, N.; van Duijn, C.M.; van Schoor, N.M.; Vitart, V.; Völker, U.; Vollenweider, P.; Völzke, H.; Wacher-Rodarte, N.H.; Walker, M.; Wang, Y.X.; Wareham, N.J.; Watanabe, R.M.; Watkins, H.; Weir, D.R.; Werge, T.M.; Widen, E.; Wilkens, L.R.; Willemsen, G.; Willett, W.C.; Wilson, J.F.; Wong, T.Y.; Woo, J.T.; Wright, A.F.; Wu, J.Y.; Xu, H.; Yajnik, C.S.; Yokota, M.; Yuan, J.M.; Zeggini, E.; Zemel, B.S.; Zheng, W.; Zhu, X.; Zmuda, J.M.; Zonderman, A.B.; Zwart, J.A.; 23andMe Research Team; VA Million Veteran Program.; DiscovEHR (DiscovEHR and MyCode Community Health Initiative).; eMERGE (Electronic Medical Records and Genomics Network).; Lifelines Cohort Study.; PRACTICAL Consortium.; Understanding Society Scientific Group.; Chasman, D.I.; Cho, Y.S.; Heid, I.M.; McCarthy, M.I.; Ng, M.C.Y.; O'Donnell, C.J.; Rivadeneira, F.; Thorsteinsdottir, U.; Sun, Y.V.; Tai, E.S.; Boehnke, M.; Deloukas, P.; Justice, A.E.; Lindgren, C.M.; Loos, R.J.F.; Mohlke, K.L.; North, K.E.; Stefansson, K.; Walters R.G.v.; Winkler, T.W.; Young, K.L.; Loh, P.R.; Yang, J.; Esko, T.; Assimes, T.L.; Auton, A.; Abecasis, G.R.; Willer, C.J.; Locke, A.E.; Berndt, S.I.; Lettre, G.; Frayling, T.M.; Frayling, T.M.; Okada, Y.; Wood, A.R.; Visscher, P.M.; Hirschhorn, J.N.Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.Item Genetic drivers of heterogeneity in type 2 diabetes pathophysiology(Nature Publishing Group, 2024) Suzuki, K.; Hatzikotoulas, K.; Southam, L.; Taylor, H.J.; Yin, X.; Lorenz, K.M.; Mandla, R.; Huerta-Chagoya, A.; Melloni, G.E.M.; Kanoni, S.; Rayner, N.W.; Bocher, O.; Arruda, A.L.; Sonehara, K.; Namba, S.; Namba, S.S.K.; Preuss, M.H.; Petty, L.E.; Schroeder, P.; Vanderwerff, B.; Kals, M.; Bragg. F.; Lin, K.; Guo, X.; Zhang, W.; Yao, J.; Kim, Y.J.; Graff, M.; Takeuchi, F.; Nano, J.; Lamri, A.; Nakatochi, M.; Moon, S.; Scott, R.A.; Cook, J.P.; Lee, J.J.; Pan, I.; Taliun, D.; Parra, E.J.; Chai. J.F.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Thorleifsson, G.; Grarup, N.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Kwak, S.H.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Nongmaithem, S.S.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Brody, J.A.; Kabagambe, E.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Broadaway, K.A.; Williamson, A.; Kamali, Z.; Cui, J.; Thangam, M.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Ahluwalia, T.S.; Anand, S.S.; Bertoni, A.; Bork-Jensen, J.; Brandslund, I.; Buchanan, T.A.; Burant, C.F.; Butterworth, A.S.; Canouil, M.; Chan, J.C.N.; Chang, L.C.; Chee, M.L.; Chen, J.; Chen, S.H.; Chen, Y.T.; Chen, Z.; Chuang, L.M.; Cushman, M.; Danesh, J.; Das, S.K.; de Silva, H.J.; Dedoussis, G.; Dimitrov, L.; Doumatey, A.P.; Du, S.; Duan, Q.; Eckardt, K.U.; Emery, L.S.; Evans, D.S.; Evans, M.K.; Fischer, K.; Floyd, J.S.; Ford, I.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; González-Villalpando, C.; González-Villalpando, M.E.; Gordon-Larsen, P.; Gross, M.; Guare, L.A.; Hackinger, S.; Hakaste, L.; Han, S.; Hattersley, A.T.; Herder, C.; Horikoshi, M.; Howard, A.; Hsueh, W.; Huang, M.; Huang, W.; Hung, Y.; Hwang, M.Y.; Hwu, C.; Ichihara, S.; Ikram, M.A.; Ingelsson, M.; Islam, M.T.; Isono, M.; Jang, H.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, T.; Kamanu, F.K.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi,T.; Keaton, J.M.; Kho, A.N.; Khor, C.; Kibriya, M.G.; Kim, D.; Kronenberg, F.; Kuusisto , J.; Läll, K.; Lange, L.A.; Lee, K.M.; Lee, M.; Lee, N.R.; Leong, A.; Li, L.; Li, Y.; Li-Gao, R.; Ligthart, S.; Lindgren, C.M.; Linneberg, A.; Liu, C.; Liu, J.; Locke, A.E.; Louie, T.; Luan, J.; Luk, A.O.; Luo, X.; Lv, J.; Lynch, J.A.; Lyssenko, V.; Maeda, S.; Mamakou, V.; Mansuri, S.R.; Matsuda, K.; Meitinger, T.; Melander, O.; Metspalu, A.; Mo, H.; Morris, A.D.; Moura, F.A.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Patil, S.; Pei, P.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Polikowsky, H.G.; Porneala, B.; Prasad, G.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sandow, K.; Sankareswaran , A.; Sattar,N.; Schönherr, S.; Shahriar, M.; Shen , B.; Shi, J.; Shin, D.M.; Shojima, N.; Smith, J.A.; So, W.Y.; Stančáková, A.; Steinthorsdottir, V.; Stilp, A.M.; Strauch, K.; Taylor, K.D.; Thorand, B.; Thorsteinsdottir, U.; Tomlinson, B.; Tran, T.C.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler , M.S.; Valladares-Salgado, A.; Dam, R.M.V.; Klinken, J.B.V.; Varma, R.; Wacher-Rodarte, N.; Wheeler,E.; Wickremasinghe, A.R.; Dijk, K.W.V.; Witte, D.R.; Yajnik, C.S.; Yamamoto, K.; Yamamoto, K.; Yoon, K.; Yu, C.; Yuan, J.; Yusuf, S.; Zawistowski, M.; Zhang, L.; Zheng, W.; Raffel, L.J.; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Fornage, .M.; Hanis, C.L.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker,D.M.; Matsuda,F.; Liu, Y.; Yokota,M.; Kardia, S.L.R.; Peyser, P.A.; Pankow, J.S.; Engert, J.C.; Bonnefond, A.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Wu, J.; Hayes, M.G.; Ma, R.C.W.; Wong, T.; Mook-Kanamori, D.O.; Tuomi, T.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu , X.; Park, K.; Jukema, J.W.; Cruz, M.; Chen, Y.I.; Rich, S.S.; McKean-Cowdin, R.; Grallert, H.; Cheng, C.; Ghanbari,M.; Tai , E.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.; Bowden, D.W.; Palmer, C.N.A.; Kooner, J.S.; Kooperberg, C.; Liu, S.; North, K.E.; Saleheen, D.; Hansen, T.; Pedersen, O.; Wareham, N.J.; Lee, J.; Kim, B.; Millwood , I.Y.; Walters, R.G.; Stefansson, K.; Ahlqvist, E.; Goodarzi, M.O.; Mohlke, K.L.; Langenberg, C.; Haiman, C.A.; Loos, R.J.F.; Florez, J.C.; Rader, D.J.; Ritchie, M.D.; Zöllner, S.; Mägi, R.; Marston, N.A.; Ruff, C.T.; Heel , D.A.V.; Finer, S.; Denny, J.C.; Yamauchi, T.; Kadowaki, T.; Chambers, J.C.; Ng, M.C.Y.; Sim, X.; Below, J.E.; Tsao, P.S.; Chang, K.; McCarthy, M.I.; Meigs, J.B.; Mahajan, A.; Spracklen, C.N.; Mercader, J.M.; Boehnke, M.; Rotter, J.I.; Vujkovic, M.; Voight, B.F.; Morris, A.P.; Zeggini, E.Type 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.