dc.contributor.author | Suzuki, K. | |
dc.contributor.author | Hatzikotoulas, K. | |
dc.contributor.author | Southam, L. | |
dc.contributor.author | Taylor, H.J. | |
dc.contributor.author | Yin, X. | |
dc.contributor.author | Lorenz, K.M. | |
dc.contributor.author | Mandla, R. | |
dc.contributor.author | Huerta-Chagoya, A. | |
dc.contributor.author | Melloni, G.E.M. | |
dc.contributor.author | Kanoni, S. | |
dc.contributor.author | Rayner, N.W. | |
dc.contributor.author | Bocher, O. | |
dc.contributor.author | Arruda, A.L. | |
dc.contributor.author | Sonehara, K. | |
dc.contributor.author | Namba, S. | |
dc.contributor.author | Namba, S.S.K. | |
dc.contributor.author | Preuss, M.H. | |
dc.contributor.author | Petty, L.E. | |
dc.contributor.author | Schroeder, P. | |
dc.contributor.author | Vanderwerff, B. | |
dc.contributor.author | Kals, M. | |
dc.contributor.author | Bragg. F. | |
dc.contributor.author | Lin, K. | |
dc.contributor.author | Guo, X. | |
dc.contributor.author | Zhang, W. | |
dc.contributor.author | Yao, J. | |
dc.contributor.author | Kim, Y.J. | |
dc.contributor.author | Graff, M. | |
dc.contributor.author | Takeuchi, F. | |
dc.contributor.author | Nano, J. | |
dc.contributor.author | Lamri, A. | |
dc.contributor.author | Nakatochi, M. | |
dc.contributor.author | Moon, S. | |
dc.contributor.author | Scott, R.A. | |
dc.contributor.author | Cook, J.P. | |
dc.contributor.author | Lee, J.J. | |
dc.contributor.author | Pan, I. | |
dc.contributor.author | Taliun, D. | |
dc.contributor.author | Parra, E.J. | |
dc.contributor.author | Chai. J.F. | |
dc.contributor.author | Bielak, L.F. | |
dc.contributor.author | Tabara, Y. | |
dc.contributor.author | Hai, Y. | |
dc.contributor.author | Thorleifsson, G. | |
dc.contributor.author | Grarup, N. | |
dc.contributor.author | Sofer, T. | |
dc.contributor.author | Wuttke, M. | |
dc.contributor.author | Sarnowski, C. | |
dc.contributor.author | Gieger, C. | |
dc.contributor.author | Nousome, D. | |
dc.contributor.author | Trompet, S. | |
dc.contributor.author | Kwak, S.H. | |
dc.contributor.author | Long, J. | |
dc.contributor.author | Sun, M. | |
dc.contributor.author | Tong, L. | |
dc.contributor.author | Chen, W.M. | |
dc.contributor.author | Nongmaithem, S.S. | |
dc.contributor.author | Noordam, R. | |
dc.contributor.author | Lim, V.J.Y. | |
dc.contributor.author | Tam, C.H.T. | |
dc.contributor.author | Joo, Y.Y. | |
dc.contributor.author | Chen, C.H. | |
dc.contributor.author | Raffield, L.M. | |
dc.contributor.author | Prins, B.P. | |
dc.contributor.author | Nicolas, A. | |
dc.contributor.author | Yanek, L.R. | |
dc.contributor.author | Chen, G. | |
dc.contributor.author | Brody, J.A. | |
dc.contributor.author | Kabagambe, E. | |
dc.contributor.author | An, P. | |
dc.contributor.author | Xiang, A.H. | |
dc.contributor.author | Choi, H.S. | |
dc.contributor.author | Cade, B.E. | |
dc.contributor.author | Tan, J. | |
dc.contributor.author | Broadaway, K.A. | |
dc.contributor.author | Williamson, A. | |
dc.contributor.author | Kamali, Z. | |
dc.contributor.author | Cui, J. | |
dc.contributor.author | Thangam, M. | |
dc.contributor.author | Adair, L.S. | |
dc.contributor.author | Adeyemo, A. | |
dc.contributor.author | Aguilar-Salinas, C.A. | |
dc.contributor.author | Ahluwalia, T.S. | |
dc.contributor.author | Anand, S.S. | |
dc.contributor.author | Bertoni, A. | |
dc.contributor.author | Bork-Jensen, J. | |
dc.contributor.author | Brandslund, I. | |
dc.contributor.author | Buchanan, T.A. | |
dc.contributor.author | Burant, C.F. | |
dc.contributor.author | Butterworth, A.S. | |
dc.contributor.author | Canouil, M. | |
dc.contributor.author | Chan, J.C.N. | |
dc.contributor.author | Chang, L.C. | |
dc.contributor.author | Chee, M.L. | |
dc.contributor.author | Chen, J. | |
dc.contributor.author | Chen, S.H. | |
dc.contributor.author | Chen, Y.T. | |
dc.contributor.author | Chen, Z. | |
dc.contributor.author | Chuang, L.M. | |
dc.contributor.author | Cushman, M. | |
dc.contributor.author | Danesh, J. | |
dc.contributor.author | Das, S.K. | |
dc.contributor.author | de Silva, H.J. | |
dc.contributor.author | Dedoussis, G. | |
dc.contributor.author | Dimitrov, L. | |
dc.contributor.author | Doumatey, A.P. | |
dc.contributor.author | Du, S. | |
dc.contributor.author | Duan, Q. | |
dc.contributor.author | Eckardt, K.U. | |
dc.contributor.author | Emery, L.S. | |
dc.contributor.author | Evans, D.S. | |
dc.contributor.author | Evans, M.K. | |
dc.contributor.author | Fischer, K. | |
dc.contributor.author | Floyd, J.S. | |
dc.contributor.author | Ford, I. | |
dc.contributor.author | Franco, O.H. | |
dc.contributor.author | Frayling, T.M. | |
dc.contributor.author | Freedman, B.I. | |
dc.contributor.author | Genter, P. | |
dc.contributor.author | Gerstein, H.C. | |
dc.contributor.author | Giedraitis, V. | |
dc.contributor.author | González-Villalpando, C. | |
dc.contributor.author | González-Villalpando, M.E. | |
dc.contributor.author | Gordon-Larsen, P. | |
dc.contributor.author | Gross, M. | |
dc.contributor.author | Guare, L.A. | |
dc.contributor.author | Hackinger, S. | |
dc.contributor.author | Hakaste, L. | |
dc.contributor.author | Han, S. | |
dc.contributor.author | Hattersley, A.T. | |
dc.contributor.author | Herder, C. | |
dc.contributor.author | Horikoshi, M. | |
dc.contributor.author | Howard, A. | |
dc.contributor.author | Hsueh, W. | |
dc.contributor.author | Huang, M. | |
dc.contributor.author | Huang, W. | |
dc.contributor.author | Hung, Y. | |
dc.contributor.author | Hwang, M.Y. | |
dc.contributor.author | Hwu, C. | |
dc.contributor.author | Ichihara, S. | |
dc.contributor.author | Ikram, M.A. | |
dc.contributor.author | Ingelsson, M. | |
dc.contributor.author | Islam, M.T. | |
dc.contributor.author | Isono, M. | |
dc.contributor.author | Jang, H. | |
dc.contributor.author | Jasmine, F. | |
dc.contributor.author | Jiang, G. | |
dc.contributor.author | Jonas, J.B. | |
dc.contributor.author | Jørgensen, T. | |
dc.contributor.author | Kamanu, F.K. | |
dc.contributor.author | Kandeel, F.R. | |
dc.contributor.author | Kasturiratne, A. | |
dc.contributor.author | Katsuya, T. | |
dc.contributor.author | Kaur, V. | |
dc.contributor.author | Kawaguchi,T. | |
dc.contributor.author | Keaton, J.M. | |
dc.contributor.author | Kho, A.N. | |
dc.contributor.author | Khor, C. | |
dc.contributor.author | Kibriya, M.G. | |
dc.contributor.author | Kim, D. | |
dc.contributor.author | Kronenberg, F. | |
dc.contributor.author | Kuusisto , J. | |
dc.contributor.author | Läll, K. | |
dc.contributor.author | Lange, L.A. | |
dc.contributor.author | Lee, K.M. | |
dc.contributor.author | Lee, M. | |
dc.contributor.author | Lee, N.R. | |
dc.contributor.author | Leong, A. | |
dc.contributor.author | Li, L. | |
dc.contributor.author | Li, Y. | |
dc.contributor.author | Li-Gao, R. | |
dc.contributor.author | Ligthart, S. | |
dc.contributor.author | Lindgren, C.M. | |
dc.contributor.author | Linneberg, A. | |
dc.contributor.author | Liu, C. | |
dc.contributor.author | Liu, J. | |
dc.contributor.author | Locke, A.E. | |
dc.contributor.author | Louie, T. | |
dc.contributor.author | Luan, J. | |
dc.contributor.author | Luk, A.O. | |
dc.contributor.author | Luo, X. | |
dc.contributor.author | Lv, J. | |
dc.contributor.author | Lynch, J.A. | |
dc.contributor.author | Lyssenko, V. | |
dc.contributor.author | Maeda, S. | |
dc.contributor.author | Mamakou, V. | |
dc.contributor.author | Mansuri, S.R. | |
dc.contributor.author | Matsuda, K. | |
dc.contributor.author | Meitinger, T. | |
dc.contributor.author | Melander, O. | |
dc.contributor.author | Metspalu, A. | |
dc.contributor.author | Mo, H. | |
dc.contributor.author | Morris, A.D. | |
dc.contributor.author | Moura, F.A. | |
dc.contributor.author | Nadler, J.L. | |
dc.contributor.author | Nalls, M.A. | |
dc.contributor.author | Nayak, U. | |
dc.contributor.author | Ntalla, I. | |
dc.contributor.author | Okada, Y. | |
dc.contributor.author | Orozco, L. | |
dc.contributor.author | Patel, S.R. | |
dc.contributor.author | Patil, S. | |
dc.contributor.author | Pei, P. | |
dc.contributor.author | Pereira, M.A. | |
dc.contributor.author | Peters, A. | |
dc.contributor.author | Pirie, F.J. | |
dc.contributor.author | Polikowsky, H.G. | |
dc.contributor.author | Porneala, B. | |
dc.contributor.author | Prasad, G. | |
dc.contributor.author | Rasmussen-Torvik, L.J. | |
dc.contributor.author | Reiner, A.P. | |
dc.contributor.author | Roden, M. | |
dc.contributor.author | Rohde, R. | |
dc.contributor.author | Roll, K. | |
dc.contributor.author | Sabanayagam, C. | |
dc.contributor.author | Sandow, K. | |
dc.contributor.author | Sankareswaran , A. | |
dc.contributor.author | Sattar,N. | |
dc.contributor.author | Schönherr, S. | |
dc.contributor.author | Shahriar, M. | |
dc.contributor.author | Shen , B. | |
dc.contributor.author | Shi, J. | |
dc.contributor.author | Shin, D.M. | |
dc.contributor.author | Shojima, N. | |
dc.contributor.author | Smith, J.A. | |
dc.contributor.author | So, W.Y. | |
dc.contributor.author | Stančáková, A. | |
dc.contributor.author | Steinthorsdottir, V. | |
dc.contributor.author | Stilp, A.M. | |
dc.contributor.author | Strauch, K. | |
dc.contributor.author | Taylor, K.D. | |
dc.contributor.author | Thorand, B. | |
dc.contributor.author | Thorsteinsdottir, U. | |
dc.contributor.author | Tomlinson, B. | |
dc.contributor.author | Tran, T.C. | |
dc.contributor.author | Tsai, F. | |
dc.contributor.author | Tuomilehto, J. | |
dc.contributor.author | Tusie-Luna, T. | |
dc.contributor.author | Udler , M.S. | |
dc.contributor.author | Valladares-Salgado, A. | |
dc.contributor.author | Dam, R.M.V. | |
dc.contributor.author | Klinken, J.B.V. | |
dc.contributor.author | Varma, R. | |
dc.contributor.author | Wacher-Rodarte, N. | |
dc.contributor.author | Wheeler,E. | |
dc.contributor.author | Wickremasinghe, A.R. | |
dc.contributor.author | Dijk, K.W.V. | |
dc.contributor.author | Witte, D.R. | |
dc.contributor.author | Yajnik, C.S. | |
dc.contributor.author | Yamamoto, K. | |
dc.contributor.author | Yamamoto, K. | |
dc.contributor.author | Yoon, K. | |
dc.contributor.author | Yu, C. | |
dc.contributor.author | Yuan, J. | |
dc.contributor.author | Yusuf, S. | |
dc.contributor.author | Zawistowski, M. | |
dc.contributor.author | Zhang, L. | |
dc.contributor.author | Zheng, W. | |
dc.contributor.author | Raffel, L.J. | |
dc.contributor.author | Igase, M. | |
dc.contributor.author | Ipp, E. | |
dc.contributor.author | Redline, S. | |
dc.contributor.author | Cho, Y.S. | |
dc.contributor.author | Lind, L. | |
dc.contributor.author | Province, M.A. | |
dc.contributor.author | Fornage, .M. | |
dc.contributor.author | Hanis, C.L. | |
dc.contributor.author | Ingelsson, E. | |
dc.contributor.author | Zonderman, A.B. | |
dc.contributor.author | Psaty, B.M. | |
dc.contributor.author | Wang, Y. | |
dc.contributor.author | Rotimi, C.N. | |
dc.contributor.author | Becker,D.M. | |
dc.contributor.author | Matsuda,F. | |
dc.contributor.author | Liu, Y. | |
dc.contributor.author | Yokota,M. | |
dc.contributor.author | Kardia, S.L.R. | |
dc.contributor.author | Peyser, P.A. | |
dc.contributor.author | Pankow, J.S. | |
dc.contributor.author | Engert, J.C. | |
dc.contributor.author | Bonnefond, A. | |
dc.contributor.author | Froguel, P. | |
dc.contributor.author | Wilson, J.G. | |
dc.contributor.author | Sheu, W.H.H. | |
dc.contributor.author | Wu, J. | |
dc.contributor.author | Hayes, M.G. | |
dc.contributor.author | Ma, R.C.W. | |
dc.contributor.author | Wong, T. | |
dc.contributor.author | Mook-Kanamori, D.O. | |
dc.contributor.author | Tuomi, T. | |
dc.contributor.author | Chandak, G.R. | |
dc.contributor.author | Collins, F.S. | |
dc.contributor.author | Bharadwaj, D. | |
dc.contributor.author | Paré, G. | |
dc.contributor.author | Sale, M.M. | |
dc.contributor.author | Ahsan, H. | |
dc.contributor.author | Motala, A.A. | |
dc.contributor.author | Shu , X. | |
dc.contributor.author | Park, K. | |
dc.contributor.author | Jukema, J.W. | |
dc.contributor.author | Cruz, M. | |
dc.contributor.author | Chen, Y.I. | |
dc.contributor.author | Rich, S.S. | |
dc.contributor.author | McKean-Cowdin, R. | |
dc.contributor.author | Grallert, H. | |
dc.contributor.author | Cheng, C. | |
dc.contributor.author | Ghanbari,M. | |
dc.contributor.author | Tai , E. | |
dc.contributor.author | Dupuis, J. | |
dc.contributor.author | Kato, N. | |
dc.contributor.author | Laakso, M. | |
dc.contributor.author | Köttgen, A. | |
dc.contributor.author | Koh, W. | |
dc.contributor.author | Bowden, D.W. | |
dc.contributor.author | Palmer, C.N.A. | |
dc.contributor.author | Kooner, J.S. | |
dc.contributor.author | Kooperberg, C. | |
dc.contributor.author | Liu, S. | |
dc.contributor.author | North, K.E. | |
dc.contributor.author | Saleheen, D. | |
dc.contributor.author | Hansen, T. | |
dc.contributor.author | Pedersen, O. | |
dc.contributor.author | Wareham, N.J. | |
dc.contributor.author | Lee, J. | |
dc.contributor.author | Kim, B. | |
dc.contributor.author | Millwood , I.Y. | |
dc.contributor.author | Walters, R.G. | |
dc.contributor.author | Stefansson, K. | |
dc.contributor.author | Ahlqvist, E. | |
dc.contributor.author | Goodarzi, M.O. | |
dc.contributor.author | Mohlke, K.L. | |
dc.contributor.author | Langenberg, C. | |
dc.contributor.author | Haiman, C.A. | |
dc.contributor.author | Loos, R.J.F. | |
dc.contributor.author | Florez, J.C. | |
dc.contributor.author | Rader, D.J. | |
dc.contributor.author | Ritchie, M.D. | |
dc.contributor.author | Zöllner, S. | |
dc.contributor.author | Mägi, R. | |
dc.contributor.author | Marston, N.A. | |
dc.contributor.author | Ruff, C.T. | |
dc.contributor.author | Heel , D.A.V. | |
dc.contributor.author | Finer, S. | |
dc.contributor.author | Denny, J.C. | |
dc.contributor.author | Yamauchi, T. | |
dc.contributor.author | Kadowaki, T. | |
dc.contributor.author | Chambers, J.C. | |
dc.contributor.author | Ng, M.C.Y. | |
dc.contributor.author | Sim, X. | |
dc.contributor.author | Below, J.E. | |
dc.contributor.author | Tsao, P.S. | |
dc.contributor.author | Chang, K. | |
dc.contributor.author | McCarthy, M.I. | |
dc.contributor.author | Meigs, J.B. | |
dc.contributor.author | Mahajan, A. | |
dc.contributor.author | Spracklen, C.N. | |
dc.contributor.author | Mercader, J.M. | |
dc.contributor.author | Boehnke, M. | |
dc.contributor.author | Rotter, J.I. | |
dc.contributor.author | Vujkovic, M. | |
dc.contributor.author | Voight, B.F. | |
dc.contributor.author | Morris, A.P. | |
dc.contributor.author | Zeggini, E. | |
dc.date.issued | 2024 | en |
dc.identifier.citation | Nature. 2024; 627(8003):347-357 [Epub. 2024 Feb 19] | en |
dc.identifier.issn | 0028-0836 (Print) | en |
dc.identifier.issn | 1476-4687 (Electronic) | en |
dc.identifier.uri | http://repository.kln.ac.lk/handle/123456789/27630 | en |
dc.description | Indexed in MEDLINE | |
dc.description.abstract | 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. | en |
dc.language | English | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | type 2 diabetes | en |
dc.title | Genetic drivers of heterogeneity in type 2 diabetes pathophysiology | |
dc.type | Article | en |