Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Mahajan, A.; Spracklen, C.N.; Zhang, W.; Ng, M.C.Y.; Petty, L.E.; Kitajima, H.; Yu, G.Z.; Rüeger, S.; Speidel, L.; Kim, Y.J.; Horikoshi, M.; Mercader, J.M .; Taliun, D.; Moon, S.; Kwak, S.H.; Robertson, N.R.; Rayner, N.W.; Loh, M.; Kim, B.; Chiou, J.; Miguel-Escalada, I.; Parolo, P.D.B.; Lin, K.; Bragg, F.; Preuss, M.H.; Takeuchi, F.; Nano, J.; Guo, X.; Lamri, A.; Nakatoch, M.; Scott, R.A.; Lee, J.J.; Huerta-Chagoya, A.; Graff, M.; Chai, J.F.; Parra, E. J.; Yao, J.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Steinthorsdottir, V.; Cook, J.P.; Kals, M.; Grarup, N.; Schmidt, E.M.; Pan, I.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Ahmad, M.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Lecoeur, C.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Jensen, R.A.; Tajuddin, S.; Kabagambe, E.K.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Flanagan, J.; Abaitua, F.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Akiyama, M.; Anand, S.S.; Bertoni, A.; Bian, Z.; Bork-Jensen, J.; Brandslund, I.; Brody, J.A.; Brummett, C.M.; Buchanan, T.A.; 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.; 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.; Fornage, M.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Fuchsberger, C.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; Villalpando, C.G.; Villalpando, M.E.G.; Goodarzi, M.O.; Larsen, P.G.; Gorkin, D.; Gross, M.; Guo, Y.; Hackinger, S.; Han, S.; Hattersley, A.T.; Herder, C.; Howard, A.G.; 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.M.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, M.E.; Jørgensen, T.; Kamatani, Y.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi, T.; Keaton, J.M.; Kho, A.N.; Khor, C.C.; Kibriya, M.G.; Kim, D.H.; Kohara, K.; Kriebel, J.; Kronenberg, F.; Kuusisto, J.; Läll, K.; Lange, L.A.; 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.; Lyssenko, V.; Mamakou, V.; Mani, K.R.; Meitinger, T.; Metspalu, A.; Morris, A.D.; Nadkarni, G.N.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Nongmaithem, S.S.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Porneala, B.; Prasad, G.; Preissl, S.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sander, M.; Sandow, K.; Sattar, N.; Schönherr, S.; Schurmann, C.; Shahriar, M.; Shi, J.; Shin, D.M.; Shriner, D.; Smith, J.A.; So, W.Y.; Stančáková, A.; Stilp, A.M.; Strauch, K.; Suzuki, K.; Takahashi, A.; Taylor, K.D.; Thorand, B.; Thorleifsson, G.; Thorsteinsdottir, U.; Tomlinson, B.; Torres, J.M.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler, M.S.; Salgado, A.V.; Dam, R.M.; Klinken, J.B.; Varma, R.; Vujkovic, M.; Wacher-Rodarte, N.; Wheeler, E.; Whitsel, E.A.; Wickremasinghe, A.R.; Dijk, K.W.; Witte, D.R.; Yajnik, C.S; Yamamoto, K.; Yamauchi, T.; Yengo, L.; Yoon, K.; Yu, C.; Yuan, J.M.; Yusuf, S.; Zhang, L.; Zheng, W.; FinnGen; eMERGE Consortium; Leslie J Raffel; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Hanis, C.L.; Peyser, P.A.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker, D.M.; Matsuda, F.; Liu, Y.; Zeggini, E.; Yokota, M.; Rich, S.S.; Kooperberg, C.; Pankow, J.S.; Engert, J.C.; Chen, Y.I.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Kardia, S.L.R.; Wu, J.Y.; Hayes, M.G.; Ma, R.C.W.; Wong, T.Y.; Groop, L.; Mook-Kanamori, D.O.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu, X.O.; Park, K.S.; Jukema, J.W.; Cruz, M.; Cowdin, R.M.; Grallert, H.; Cheng, C.Y.; Bottinger, E.P.; Dehghan, A.; Tai, E.S.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.P.; Palmer, C.N.A.; Liu, S.; Abecasis, G.; Kooner, J.S.; Loos, R.J.F.; North, K.E.; Haiman, C.A.; Florez, J.C.; Saleheen, D.; Hansen, T.; Pedersen, O.; Mägi, R.; Langenberg, C.; Wareham, N.J.; Maeda, S.; Kadowaki, T.; Lee, J.; Millwood, I.Y.; Walters, R.G.; Stefansson, K.; Myers, S.R.; Ferrer, J.; Gaulton, K.J.; Meigs, J.B.; Mohlke, K.L.; Gloyn, A.L.; Bowden, D.W.; Below, J.E.; Chambers, J.C.; Sim, X.; Boehnke, M.; Rotter, J.I.; McCarthy, M.I.; Morris, A.P.

dc.contributor.author	Mahajan, A.
dc.contributor.author	Spracklen, C.N.
dc.contributor.author	Zhang, W.
dc.contributor.author	Ng, M.C.Y.
dc.contributor.author	Petty, L.E.
dc.contributor.author	Kitajima, H.
dc.contributor.author	Yu, G.Z.
dc.contributor.author	Rüeger, S.
dc.contributor.author	Speidel, L.
dc.contributor.author	Kim, Y.J.
dc.contributor.author	Horikoshi, M.
dc.contributor.author	Mercader, J.M .
dc.contributor.author	Taliun, D.
dc.contributor.author	Moon, S.
dc.contributor.author	Kwak, S.H.
dc.contributor.author	Robertson, N.R.
dc.contributor.author	Rayner, N.W.
dc.contributor.author	Loh, M.
dc.contributor.author	Kim, B.
dc.contributor.author	Chiou, J.
dc.contributor.author	Miguel-Escalada, I.
dc.contributor.author	Parolo, P.D.B.
dc.contributor.author	Lin, K.
dc.contributor.author	Bragg, F.
dc.contributor.author	Preuss, M.H.
dc.contributor.author	Takeuchi, F.
dc.contributor.author	Nano, J.
dc.contributor.author	Guo, X.
dc.contributor.author	Lamri, A.
dc.contributor.author	Nakatoch, M.
dc.contributor.author	Scott, R.A.
dc.contributor.author	Lee, J.J.
dc.contributor.author	Huerta-Chagoya, A.
dc.contributor.author	Graff, M.
dc.contributor.author	Chai, J.F.
dc.contributor.author	Parra, E. J.
dc.contributor.author	Yao, J.
dc.contributor.author	Bielak, L.F.
dc.contributor.author	Tabara, Y.
dc.contributor.author	Hai, Y.
dc.contributor.author	Steinthorsdottir, V.
dc.contributor.author	Cook, J.P.
dc.contributor.author	Kals, M.
dc.contributor.author	Grarup, N.
dc.contributor.author	Schmidt, E.M.
dc.contributor.author	Pan, I.
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	Long, J.
dc.contributor.author	Sun, M.
dc.contributor.author	Tong, L.
dc.contributor.author	Chen, W.M.
dc.contributor.author	Ahmad, M.
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	Lecoeur, C.
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	Jensen, R.A.
dc.contributor.author	Tajuddin, S.
dc.contributor.author	Kabagambe, E.K.
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	Flanagan, J.
dc.contributor.author	Abaitua, F.
dc.contributor.author	Adair, L.S.
dc.contributor.author	Adeyemo, A.
dc.contributor.author	Aguilar-Salinas, C.A.
dc.contributor.author	Akiyama, M.
dc.contributor.author	Anand, S.S.
dc.contributor.author	Bertoni, A.
dc.contributor.author	Bian, Z.
dc.contributor.author	Bork-Jensen, J.
dc.contributor.author	Brandslund, I.
dc.contributor.author	Brody, J.A.
dc.contributor.author	Brummett, C.M.
dc.contributor.author	Buchanan, T.A.
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	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.
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dc.contributor.author	Eckardt, K.U.
dc.contributor.author	Emery, L.S.
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dc.contributor.author	Evans, M.K.
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dc.contributor.author	Fornage, M.
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dc.contributor.author	Giedraitis, V.
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dc.contributor.author	Villalpando, M.E.G.
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dc.contributor.author	Larsen, P.G.
dc.contributor.author	Gorkin, D.
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dc.contributor.author	Ingelsson, M.
dc.contributor.author	Islam, M.T.
dc.contributor.author	Isono, M.
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dc.contributor.author	Jasmine, F.
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dc.contributor.author	Jonas, J.B.
dc.contributor.author	Jørgensen, M.E.
dc.contributor.author	Jørgensen, T.
dc.contributor.author	Kamatani, Y.
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.C.
dc.contributor.author	Kibriya, M.G.
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dc.contributor.author	Kohara, K.
dc.contributor.author	Kriebel, J.
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, 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.
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dc.contributor.author	Louie, T.
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dc.contributor.author	Morris, A.D.
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dc.contributor.author	Takahashi, A.
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dc.contributor.author	Thorsteinsdottir, U.
dc.contributor.author	Tomlinson, B.
dc.contributor.author	Torres, J.M.
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	Salgado, A.V.
dc.contributor.author	Dam, R.M.
dc.contributor.author	Klinken, J.B.
dc.contributor.author	Varma, R.
dc.contributor.author	Vujkovic, M.
dc.contributor.author	Wacher-Rodarte, N.
dc.contributor.author	Wheeler, E.
dc.contributor.author	Whitsel, E.A.
dc.contributor.author	Wickremasinghe, A.R.
dc.contributor.author	Dijk, K.W.
dc.contributor.author	Witte, D.R.
dc.contributor.author	Yajnik, C.S
dc.contributor.author	Yamamoto, K.
dc.contributor.author	Yamauchi, T.
dc.contributor.author	Yengo, L.
dc.contributor.author	Yoon, K.
dc.contributor.author	Yu, C.
dc.contributor.author	Yuan, J.M.
dc.contributor.author	Yusuf, S.
dc.contributor.author	Zhang, L.
dc.contributor.author	Zheng, W.
dc.contributor.author	FinnGen; eMERGE Consortium; Leslie J Raffel
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	Hanis, C.L.
dc.contributor.author	Peyser, P.A.
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.
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dc.contributor.author	Matsuda, F.
dc.contributor.author	Liu, Y.
dc.contributor.author	Zeggini, E.
dc.contributor.author	Yokota, M.
dc.contributor.author	Rich, S.S.
dc.contributor.author	Kooperberg, C.
dc.contributor.author	Pankow, J.S.
dc.contributor.author	Engert, J.C.
dc.contributor.author	Chen, Y.I.
dc.contributor.author	Froguel, P.
dc.contributor.author	Wilson, J.G.
dc.contributor.author	Sheu, W.H.H.
dc.contributor.author	Kardia, S.L.R.
dc.contributor.author	Wu, J.Y.
dc.contributor.author	Hayes, M.G.
dc.contributor.author	Ma, R.C.W.
dc.contributor.author	Wong, T.Y.
dc.contributor.author	Groop, L.
dc.contributor.author	Mook-Kanamori, D.O.
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.O.
dc.contributor.author	Park, K.S.
dc.contributor.author	Jukema, J.W.
dc.contributor.author	Cruz, M.
dc.contributor.author	Cowdin, R.M.
dc.contributor.author	Grallert, H.
dc.contributor.author	Cheng, C.Y.
dc.contributor.author	Bottinger, E.P.
dc.contributor.author	Dehghan, A.
dc.contributor.author	Tai, E.S.
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.P.
dc.contributor.author	Palmer, C.N.A.
dc.contributor.author	Liu, S.
dc.contributor.author	Abecasis, G.
dc.contributor.author	Kooner, J.S.
dc.contributor.author	Loos, R.J.F.
dc.contributor.author	North, K.E.
dc.contributor.author	Haiman, C.A.
dc.contributor.author	Florez, J.C.
dc.contributor.author	Saleheen, D.
dc.contributor.author	Hansen, T.
dc.contributor.author	Pedersen, O.
dc.contributor.author	Mägi, R.
dc.contributor.author	Langenberg, C.
dc.contributor.author	Wareham, N.J.
dc.contributor.author	Maeda, S.
dc.contributor.author	Kadowaki, T.
dc.contributor.author	Lee, J.
dc.contributor.author	Millwood, I.Y.
dc.contributor.author	Walters, R.G.
dc.contributor.author	Stefansson, K.
dc.contributor.author	Myers, S.R.
dc.contributor.author	Ferrer, J.
dc.contributor.author	Gaulton, K.J.
dc.contributor.author	Meigs, J.B.
dc.contributor.author	Mohlke, K.L.
dc.contributor.author	Gloyn, A.L.
dc.contributor.author	Bowden, D.W.
dc.contributor.author	Below, J.E.
dc.contributor.author	Chambers, J.C.
dc.contributor.author	Sim, X.
dc.contributor.author	Boehnke, M.
dc.contributor.author	Rotter, J.I.
dc.contributor.author	McCarthy, M.I.
dc.contributor.author	Morris, A.P.
dc.date.accessioned	2022-06-03T06:15:47Z
dc.date.available	2022-06-03T06:15:47Z
dc.date.issued	2022
dc.identifier.citation	Nature Genetics.2022;54(5):560-572.	en_US
dc.identifier.issn	1061-4036
dc.identifier.uri	http://repository.kln.ac.lk/handle/123456789/24629
dc.description	Indexed in MEDLINE.	en_US
dc.description.abstract	We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.	en_US
dc.language.iso	en	en_US
dc.publisher	Nature Publishing Company, New York	en_US
dc.subject	Diabetes	en_US
dc.subject	Populations	en_US
dc.title	Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation	en_US
dc.type	Article	en_US

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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

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