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

作者：Anubha Mahajan, Cassandra Nichole Spracklen, Weihua Zhang, Maggie C. Y. Ng, Lauren E. Petty, Hidetoshi Kitajima, Grace Zhuo Yu, Sina Rüeger, Leo Speidel, Young Jin Kim, Momoko Horikoshi, Josep Maria Mercader, Daniel Taliun, Sanghoon Moon, Soo‐Heon Kwak, Neil R. Robertson, Nigel William Rayner, Marie Chiew Shia Loh, Bong-Jo Kim, Joshua Chiou, Irene Miguel-Escalada, Pietro Della Briotta Parolo, Kuang Lin, Fiona Bragg, Michael Preuß, Fumihiko Takeuchi, Jana Nano, Xiuqing Guo, Amel Lamri, Masahiro Nakatochi, Robert A. Scott, Jung‐Jin Lee, Alicia Huerta‐Chagoya, Mariaelisa Graff, Jin Fang Chai, Esteban Juan Parra, Jie Yao, Lawrence F. Bielak, Yasuharu Tabara, Yang Hai, Valgerður Steinthórsdóttir, James P. Cook, Mart Kals, Niels Grarup, Ellen M. Schmidt, Ian Pan, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Jirong Long, Meng Sun, Tong Lin, Wei‐Min Chen, Meraj Ahmad, Raymond Noordam, Victor Lim, Claudia H.T. Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M. Raffield, Cécile Lecoeur, Bram Peter Prins, Aude Nicolas, Lisa R. Yanek, Guanjie Chen, Richard A. Jensen, Salman M. Tajuddin, Edmond Kato Kabagambe, Ping An, Anny H. Xiang, Hyeok Sun Choi, Brian E. Cade, Jingyi Tan, Jack U. Flanagan, Fernando Abaitua, Linda S. Adair, Adebowale Adeyemo, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Sonia Savitri Anand, Alain G. Bertoni, Zheng Bian, Jette Bork‐Jensen, Ivan Brandslund, Jennifer A. Brody, Chad M. Brummett, Thomas A. Buchanan, Mickaël Canouil, Juliana C.N. Chan, Li-Ching Chang, Miao-Li Chee, Chen Ji, Shyh‐Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee‐Ming Chuang, Mary Cushman, Swapan K. Das, H Janaka de Silva, George V. Dedoussis, Latchezar M. Dimitrov, Ayo Priscille Doumatey, Shufa Du, Qing Duan, Kai‐Uwe Eckardt, Leslie S. Emery, Daniel S. Evans, Michele K. Evans, Krista Fischer, James S. Floyd, Ian Ford, Myriam Fornage, Oscar H. Franco, Timothy M. Frayling, B. I. Freedman, Christian Fuchsberger, Pauline M. Genter, Hertzel C. Gerstein, Vilmantas Giedraitis, Clicerio González‐Villalpando, María Elena González-Villalpando, Mark O. Goodarzi, Penny Gordon‐Larsen, David U. Gorkin, Myron D. Gross, Yu Guo, Sophie Hackinger, Sohee Han, Andrew Tym Hattersley, Christian Herder, Annie-Green Howard, Willa A. Hsueh, Mengna Huang, Wei Huang, Yi‐Jen Hung, Mi Yeong Hwang, Chii‐Min Hwu, Sahoko Ichihara, M. Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost Bruno Jonas, Marit E. Jørgensen, Torben Jørgensen, Yoichiro Kamatani, FOUAD R. KANDEEL, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M. Keaton, Abel Kho, Chiea Chuen Khor, Muhammad Ghulam Kibriya, Duk-Hwan Kim, Katsuhiko Kohara, Jennifer Kriebel, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A. Lange, Myung‐Shik Lee, Sang Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li‐Gao, Symen Ligthart, Cecilia M. Lindgren, Allan R Linneberg, Ching‐Ti Liu, Jianjun Liu, Adam E. Locke, Tin Louie, Jian’an Luan, Andrea O. Y. Luk, Xi Luo, Jun Lv, Valeriya Lyssenko, Vasiliki Mamakou, K. Radha Mani, Thomas Meitinger, Andres Metspalu, Andrew D. Morris, Girish N. Nadkarni, Jerry L. Nadler, Michael A. Nalls, Uma Nayak, Suraj Singh Nongmaithem, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R. Patel, Mark A. Pereira, Annette Peters, Fraser Pirie, Bianca Porneala, Gauri Prasad, Sebastian Preißl, Laura J. Rasmussen‐Torvik, Alexander P. Reiner, Michael Roden, Rebecca Rohde, Kathryn Roll, Charumathi Sabanayagam, Maike Sander, Kevin Sandow, Naveed A. Sattar, Sebastian G. Schönherr, Claudia Schurmann, Hasan Shahriar, Jinxiu Shi, Dong Mun Shin, Daniel Shriner, Jennifer A. Smith, Wing Yee So, Alena Stančáková, Adrienne M. Stilp, Konstantin Strauch, Ken Suzuki, Atsushi Takahashi, Kent D. Taylor, Barbara Thorand, Guðmar Þorleifsson, Unnur Arna Thorsteinsdottir, Brian Tomlinson, Jason Torres, Fuu‐Jen Tsai, Jaakko Tuomilehto, Teresa Tusié‐Luna, Miriam S. Udler, Adán Valladares‐Salgado, Rob M. van Dam, Jan Bert van Klinken, Rohit Varma, Marijana Vujković, Niels H. Wacher-Rodarte, Eleanor Wheeler, Eric A. Whitsel, Ananda Rajitha Wickremasinghe, Ko Willems van Dijk, Daniel R. Witte, Chittaranjan Sakerlal Yajnik, Ken Yamamoto, Toshimasa Yamauchi, Loïc Yengo, Kyungheon Yoon, Canqing Yu, Jian‐Min Yuan, Salim Yusuf, Liang Zhang, Wei Zheng, FinnGen, Sina Rüeger, Pietro Della Briotta Parolo, Yoonjung Yoonie Joo, M. Geoffrey Hayes, Leslie J. Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A. Province, Craig L. Hanis, Patricia A. Peyser, Erik Ingelsson, Alan B. Zonderman, Bruce M. Psaty, Ya Xing Wang, Charles N. Rotimi, Diane M. Becker, Fumihiko Matsuda, Ching‐Ti Liu, Eleftheria Zeggini, Mitsuhiro Yokota, Stephen S. Rich, Charles L Kooperberg, James S. Pankow, James C. Engert, Yii‐Der Ida Chen, Philippe Froguel, James Grant Wilson, Wayne H.-H. Sheu, Sharon L. R. Kardia, Jer‐Yuarn Wu, M. Geoffrey Hayes, Ronald C.W., Tien Yin Wong, Leif Groop, Dennis O. Mook‐Kanamori, Giriraj R. Chandak, Francis S. Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M. Sale, Habibul Ahsan, Ayesha Ahmed Motala, Xiao‐Ou Shu, Kyong Soo Park, J. Wouter Jukema, Miguel Cruz, Roberta McKean‐Cowdin, Harald Grallert, Ching‐Yu Cheng, Erwin P. Böttinger, Abbas Dehghan, E Shyong Tai, Josée Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon‐Puay Koh, Colin N. A. Palmer, Simin Liu, Gonçalo R. Abecasis, Jaspal S. Kooner, Ruth J. F. Loos, Kari E. North, Christopher A. Haiman, Jose C. Florez, Danish Saleheen, Torben F. Hansen, Oluf Borbye Pedersen, Reedik Mägi, Claudia Langenberg, Nicholas J. Wareham, Shiro Maeda, Takashi Kadowaki, Juyoung Lee, Iona Y. Millwood, Robin G. Walters, Kāri Stefánsson, Simon Robert Myers, Jorge P. Ferrer, Kyle J. Gaulton, James B. Meigs, Karen L. Mohlke, Anna L. Gloyn, Donald W. Bowden, Jennifer E. Below, John C. Chambers, Xueling Sim, Michael Boehnke, Jerome I. Rotter, Mark I. McCarthy, Andrew Paul Morris · 发表于：Nature Genetics · 年份：2022 · DOI：10.1038/s41588-022-01058-3 · 被引用次数：774 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Bioinformatics and Genomic Networks

), 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.