Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
Creators: name: Lim, Victor J. Y.
name: Bowden, Donald W.
name: van Dijk, Ko Willems
name: Lind, Lars
name: Brummett, Chad M.
name: Millwood, Iona Y.
name: Yuan, Jian-Min
name: Lee, Myung-Shik
name: Khor, Chiea-Chuen
name: Yao, Jie
name: Gorkin, David
name: Liu, Jianjun
name: Bertoni, Alain
name: McCarthy, Mark I.
name: Cade, Brian E.
name: Hung, Yi-Jen
name: Ford, Ian
name: Cruz, Miguel
name: Pankow, James S.
name: Doumatey, Ayo P.
name: Takahashi, Atsushi
name: Metspalu, Andres
name: Gieger, Christian
name: Long, Jirong
name: Tajuddin, Salman
name: Joo, Yoonjung Yoonie
name: Rasmussen-Torvik, Laura J.
name: Engert, James C.
name: Guo, Xiuqing
name: Canouil, Mickaël
name: Kandeel, Fouad R.
name: Witte, Daniel R.
name: Walters, Robin G.
name: Kibriya, Muhammad G.
name: Valladares-Salgado, Adan
name: Yusuf, Salim
name: Lindgren, Cecilia M.
name: Gross, Myron
name: Sandow, Kevin
name: Li, Liming
name: Taliun, Daniel
name: Tan, Jingyi
name: Bork-Jensen, Jette
name: Du, Shufa
name: Koh, Woon-Puay
name: Franco, Oscar H.
name: Hwang, Mi Yeong
name: Grallert, Harald
name: Taylor, Kent D.
name: Rotimi, Charles N.
name: Rüeger, Sina
name: Hansen, Torben
name: Shahriar, Mohammad
name: Rotter, Jerome I.
name: Sun, Meng
name: Mook-Kanamori, Dennis O.
name: van Dam, Rob M.
name: Chen, Chien-Hsiun
name: Raffel, Leslie J.
name: Sim, Xueling
name: Lamri, Amel
name: Yamamoto, Ken
name: Chan, Juliana C. N.
name: Peyser, Patricia A.
name: Myers, Simon R.
name: Luk, Andrea O.
name: Psaty, Bruce M.
name: Hai, Yang
name: Hackinger, Sophie
name: Kamatani, Yoichiro
name: Chen, Yuan-Tsong
name: Abaitua, Fernando
name: Ichihara, Sahoko
name: Frayling, Timothy M.
name: Cheng, Ching-Yu
name: Eckardt, Kai-Uwe
name: Pedersen, Oluf
name: Thorleifsson, Gudmar
name: Becker, Diane M.
name: Sarnowski, Chloe
name: Okada, Yukinori
name: Prins, Bram Peter
name: Chen, Wei-Min
name: Abecasis, Goncalo
name: Jensen, Richard A.
name: Chen, Ji
name: Lin, Kuang
name: Tam, Claudia H. T.
name: Wilson, James G.
name: Leong, Aaron
name: Scott, Robert A.
name: Kaur, Varinderpal
name: Yamauchi, Toshimasa
name: Nano, Jana
name: Ferrer, Jorge
name: Varma, Rohit
name: Orozco, Lorena
name: González-Villalpando, Clicerio
name: Han, Sohee
name: Roden, Michael
name: Ligthart, Symen
name: Schurmann, Claudia
name: Chen, Zhengming
name: Loh, Marie
name: Bielak, Lawrence F.
name: Kohara, Katsuhiko
name: Horikoshi, Momoko
name: Shin, Dong Mun
name: Das, Swapan K.
name: Lyssenko, Valeriya
name: Luan, Jian’an
name: Adair, Linda S.
name: Emery, Leslie S.
name: Liu, Yongmei
name: Thorsteinsdottir, Unnur
name: Cushman, Mary
name: So, Wing Yee
name: Moon, Sanghoon
name: Akiyama, Masato
name: Nadler, Jerry L.
name: Sale, Michèle M.
name: Park, Kyong-Soo
name: Ahmad, Meraj
name: Bharadwaj, Dwaipayan
name: Kabagambe, Edmond K.
name: Vujkovic, Marijana
name: Bragg, Fiona
name: Redline, Susan
name: Brandslund, Ivan
name: Rohde, Rebecca
name: Lee, Jung-Jin
name: Pereira, Mark A.
name: Hanis, Craig L.
name: Zhang, Liang
name: Hayes, M. Geoffrey
name: Kals, Mart
name: Shriner, Daniel
name: Wickremasinghe, Ananda R.
name: Kwak, Soo-Heon
name: Tabara, Yasuharu
name: Kriebel, Jennifer
name: Zhang, Weihua
name: Katsuya, Tomohiro
name: Giedraitis, Vilmantas
name: Kho, Abel N.
name: Aguilar-Salinas, Carlos A.
name: Li-Gao, Ruifang
name: Genter, Pauline
name: Wuttke, Matthias
name: Evans, Michele K.
name: Ikram, Mohammad Arfan
name: Stančáková, Alena
name: Jiang, Guozhi
name: Ahsan, Habibul
name: Nalls, Michael A.
name: Choi, Hyeok Sun
name: Laakso, Markku
name: Lv, Jun
name: Huang, Wei
name: Chen, Guanjie
name: Langenberg, Claudia
name: Kooperberg, Charles
name: Dimitrov, Latchezar
name: Chai, Jin-Fang
name: Takeuchi, Fumihiko
name: Wu, Jer-Yuarn
name: Ng, Maggie C. Y.
name: Tsai, Fuu-Jen
name: Yu, Canqing
name: Nakatochi, Masahiro
name: Peters, Annette
name: Gordon-Larsen, Penny
name: Trompet, Stella
name: Wong, Tien-Yin
name: Pan, Ian
name: Liu, Ching-Ti
name: Miguel-Escalada, Irene
name: Steinthorsdottir, Valgerdur
name: Kuusisto, Johanna
name: Rayner, Nigel W.
name: Kim, Duk-Hwan
name: Herder, Christian
name: Lee, Nanette R.
name: Ingelsson, Erik
name: Strauch, Konstantin
name: Tai, E-Shyong
name: Bian, Zheng
name: Nongmaithem, Suraj S.
name: Shu, Xiao-Ou
name: Nadkarni, Girish N.
name: Zeggini, Eleftheria
name: Paré, Guillaume
name: Köttgen, Anna
name: Fornage, Myriam
name: McKean-Cowdin, Roberta
name: Morris, Andrew P.
name: Wareham, Nicholas J.
name: Whitsel, Eric A.
name: Wang, Ya-Xing
name: North, Kari E.
name: Kitajima, Hidetoshi
name: Province, Michael A.
name: Buchanan, Thomas A.
name: Sander, Maike
name: Saleheen, Danish
name: Raffield, Laura M.
name: Jasmine, Farzana
name: Mohlke, Karen L.
name: Chang, Li-Ching
name: Groop, Leif
name: Chen, Yii-Der Ida
name: Zheng, Wei
name: Chambers, John C.
name: Yajnik, Chittaranjan S.
name: Stefansson, Kari
name: Cook, James P.
name: Läll, Kristi
name: Speidel, Leo
name: Keaton, Jacob M.
name: Mahajan, Anubha
name: Howard, Annie-Green
name: Kasturiratne, Anuradhani
name: Goodarzi, Mark O.
name: Zonderman, Alan B.
name: Linneberg, Allan
name: Guo, Yu
name: Shi, Jinxiu
name: Isono, Masato
name: Huang, Mengna
name: Suzuki, Ken
name: Fischer, Krista
name: Bottinger, Erwin P.
name: Dedoussis, George
name: Flanagan, Jack
name: Palmer, Colin N. A.
name: Hwu, Chii-Min
name: Mani, K. Radha
name: Luo, Xi
name: Kadowaki, Takashi
name: Duan, Qing
name: Mägi, Reedik
name: Kim, Young Jin
name: Udler, Miriam S.
name: Torres, Jason M.
name: Prasad, Gauri
name: Lecoeur, Cécile
name: Tong, Lin
name: Jørgensen, Torben
name: Gaulton, Kyle J.
name: Chee, Miao-Li
name: della Briotta Parolo, Pietro
name: Lee, Juyoung
name: Froguel, Philippe
name: Igase, Michiya
name: Boehnke, Michael
name: Chandak, Giriraj R.
name: Chiou, Joshua
name: Kronenberg, Florian
name: Petty, Lauren E.
name: Hattersley, Andrew T.
name: Thorand, Barbara
name: Ingelsson, Martin
name: Stilp, Adrienne M.
name: Dehghan, Abbas
name: Liu, Simin
name: Nayak, Uma
name: Motala, Ayesha A.
name: Meitinger, Thomas
name: Freedman, Barry I.
name: van Klinken, Jan B.
name: Florez, Jose C.
name: Matsuda, Fumihiko
name: Chuang, Lee-Ming
name: Mercader, Josep M.
name: Wheeler, Eleanor
name: Schönherr, Sebastian
name: Tuomilehto, Jaakko
name: Loos, Ruth J. F.
name: Nicolas, Aude
name: Sabanayagam, Charumathi
name: Pirie, Fraser J.
name: Huerta-Chagoya, Alicia
name: Below, Jennifer E.
name: Chen, Shyh-Huei
name: Collins, Francis S.
name: Sheu, Wayne H. H.
name: Meigs, James B.
name: Ipp, Eli
name: Yengo, Loïc
name: Louie, Tin
name: Yu, Grace Z.
name: Kawaguchi, Takahisa
name: González-Villalpando, Maria Elena
name: Locke, Adam E.
name: Grarup, Niels
name: Smith, Jennifer A.
name: Kim, Bong-Jo
name: Islam, Md Tariqul
name: An, Ping
name: Dupuis, Josée
name: Hsueh, Willa
name: Adeyemo, Adebowale
name: Ntalla, Ioanna
name: Morris, Andrew D.
name: Nousome, Darryl
name: de Silva, H. Janaka
name: Yokota, Mitsuhiro
name: Fuchsberger, Christian
name: Mamakou, Vasiliki
name: Sofer, Tamar
name: Evans, Daniel S.
name: Maeda, Shiro
name: Patel, Sanjay R.
name: Tusie-Luna, Teresa
name: Reiner, Alexander P.
name: Yanek, Lisa R.
name: Porneala, Bianca
name: Robertson, Neil R.
name: Noordam, Raymond
name: Graff, Mariaelisa
name: Gloyn, Anna L.
name: Preuss, Michael H.
name: Jørgensen, Marit E.
name: Kardia, Sharon L. R.
name: Brody, Jennifer A.
name: Yoon, Kyungheon
name: Wacher-Rodarte, Niels
name: Lange, Leslie A.
name: Li, Yun
name: Kooner, Jaspal S.
name: Cho, Yoon Shin
name: Schmidt, Ellen M.
name: Jonas, Jost B.
name: Xiang, Anny H.
name: Tomlinson, Brian
name: Anand, Sonia S.
name: Jang, Hye-Mi
name: Kato, Norihiro
name: Floyd, James S.
name: Jukema, J. Wouter
name: Gerstein, Hertzel C.
name: Rich, Stephen S.
name: Spracklen, Cassandra N.
name: Roll, Kathryn
name: Haiman, Christopher A.
name: Sattar, Naveed
name: Preissl, Sebastian
name: Ma, Ronald C. W.
name: Parra, Esteban J.
Publisher: name: Springer Nature
Year: 2022

description: <p>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&thinsp;&lt;&thinsp;5&thinsp;&times;&thinsp;10&minus;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 &gt;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.</p>