학술논문
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
Document Type
Article
Author
Mahajan, Anubha; Spracklen, Cassandra N.; Zhang, Weihua; Ng, Maggie C. Y.; Petty, Lauren E.; Kitajima, Hidetoshi; Yu, Grace Z.; Rüeger, Sina; Speidel, Leo; Kim, Young Jin; Horikoshi, Momoko; Mercader, Josep M.; Taliun, Daniel; Moon, Sanghoon; Kwak, Soo-Heon; Robertson, Neil R.; Rayner, Nigel W.; Loh, Marie; Kim, Bong-Jo; Chiou, Joshua; Miguel-Escalada, Irene; della Briotta Parolo, Pietro; Lin, Kuang; Bragg, Fiona; Preuss, Michael H.; Takeuchi, Fumihiko; Nano, Jana; Guo, Xiuqing; Lamri, Amel; Nakatochi, Masahiro; Scott, Robert A.; Lee, Jung-Jin; Huerta-Chagoya, Alicia; Graff, Mariaelisa; Chai, Jin-Fang; Parra, Esteban J.; Yao, Jie; Bielak, Lawrence F.; Tabara, Yasuharu; Hai, Yang; Steinthorsdottir, Valgerdur; Cook, James P.; Kals, Mart; Grarup, Niels; Schmidt, Ellen M.; Pan, Ian; Sofer, Tamar; Wuttke, Matthias; Sarnowski, Chloe; Gieger, Christian; Nousome, Darryl; Trompet, Stella; Long, Jirong; Sun, Meng; Tong, Lin; Chen, Wei-Min; Ahmad, Meraj; Noordam, Raymond; Lim, Victor J. Y.; Tam, Claudia H. T.; Joo, Yoonjung Yoonie; Chen, Chien-Hsiun; Raffield, Laura M.; Lecoeur, Cécile; Prins, Bram Peter; Nicolas, Aude; Yanek, Lisa R.; Chen, Guanjie; Jensen, Richard A.; Tajuddin, Salman; Kabagambe, Edmond K.; An, Ping; Xiang, Anny H.; Choi, Hyeok Sun; Cade, Brian E.; Tan, Jingyi; Flanagan, Jack; Abaitua, Fernando; Adair, Linda S.; Adeyemo, Adebowale; Aguilar-Salinas, Carlos A.; Akiyama, Masato; Anand, Sonia S.; Bertoni, Alain; Bian, Zheng; Bork-Jensen, Jette; Brandslund, Ivan; Brody, Jennifer A.; Brummett, Chad M.; Buchanan, Thomas A.; Canouil, Mickaël; Chan, Juliana C. N.; Chang, Li-Ching; Chee, Miao-Li; Chen, Ji; Chen, Shyh-Huei; Chen, Yuan-Tsong; Chen, Zhengming; Chuang, Lee-Ming; Cushman, Mary; Das, Swapan K.; de Silva, H. Janaka; Dedoussis, George; Dimitrov, Latchezar; Doumatey, Ayo P.; Du, Shufa; Duan, Qing; Eckardt, Kai-Uwe; Emery, Leslie S.; Evans, Daniel S.; Evans, Michele K.; Fischer, Krista; Floyd, James S.; Ford, Ian; Fornage, Myriam; Franco, Oscar H.; Frayling, Timothy M.; Freedman, Barry I.; Fuchsberger, Christian; Genter, Pauline; Gerstein, Hertzel C.; Giedraitis, Vilmantas; González-Villalpando, Clicerio; González-Villalpando, Maria Elena; Goodarzi, Mark O.; Gordon-Larsen, Penny; Gorkin, David; Gross, Myron; Guo, Yu; Hackinger, Sophie; Han, Sohee; Hattersley, Andrew T.; Herder, Christian; Howard, Annie-Green; Hsueh, Willa; Huang, Mengna; Huang, Wei; Hung, Yi-Jen; Hwang, Mi Yeong; Hwu, Chii-Min; Ichihara, Sahoko; Ikram, Mohammad Arfan; Ingelsson, Martin; Islam, Md Tariqul; Isono, Masato; Jang, Hye-Mi; Jasmine, Farzana; Jiang, Guozhi; Jonas, Jost B.; Jørgensen, Marit E.; Jørgensen, Torben; Kamatani, Yoichiro; Kandeel, Fouad R.; Kasturiratne, Anuradhani; Katsuya, Tomohiro; Kaur, Varinderpal; Kawaguchi, Takahisa; Keaton, Jacob M.; Kho, Abel N.; Khor, Chiea-Chuen; Kibriya, Muhammad G.; Kim, Duk-Hwan; Kohara, Katsuhiko; Kriebel, Jennifer; Kronenberg, Florian; Kuusisto, Johanna; Läll, Kristi; Lange, Leslie A.; Lee, Myung-Shik; Lee, Nanette R.; Leong, Aaron; Li, Liming; Li, Yun; Li-Gao, Ruifang; Ligthart, Symen; Lindgren, Cecilia M.; Linneberg, Allan; Liu, Ching-Ti; Liu, Jianjun; Locke, Adam E.; Louie, Tin; Luan, Jian’an; Luk, Andrea O.; Luo, Xi; Lv, Jun; Lyssenko, Valeriya; Mamakou, Vasiliki; Mani, K. Radha; Meitinger, Thomas; Metspalu, Andres; Morris, Andrew D.; Nadkarni, Girish N.; Nadler, Jerry L.; Nalls, Michael A.; Nayak, Uma; Nongmaithem, Suraj S.; Ntalla, Ioanna; Okada, Yukinori; Orozco, Lorena; Patel, Sanjay R.; Pereira, Mark A.; Peters, Annette; Pirie, Fraser J.; Porneala, Bianca; Prasad, Gauri; Preissl, Sebastian; Rasmussen-Torvik, Laura J.; Reiner, Alexander P.; Roden, Michael; Rohde, Rebecca; Roll, Kathryn; Sabanayagam, Charumathi; Sander, Maike; Sandow, Kevin; Sattar, Naveed; Schönherr, Sebastian; Schurmann, Claudia; Shahriar, Mohammad; Shi, Jinxiu; Shin, Dong Mun; Shriner, Daniel; Smith, Jennifer A.; So, Wing Yee; Stančáková, Alena; Stilp, Adrienne M.; Strauch, Konstantin; Suzuki, Ken; Takahashi, Atsushi; Taylor, Kent D.; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tomlinson, Brian; Torres, Jason M.; Tsai, Fuu-Jen; Tuomilehto, Jaakko; Tusie-Luna, Teresa; Udler, Miriam S.; Valladares-Salgado, Adan; van Dam, Rob M.; van Klinken, Jan B.; Varma, Rohit; Vujkovic, Marijana; Wacher-Rodarte, Niels; Wheeler, Eleanor; Whitsel, Eric A.; Wickremasinghe, Ananda R.; van Dijk, Ko Willems; Witte, Daniel R.; Yajnik, Chittaranjan S.; Yamamoto, Ken; Yamauchi, Toshimasa; Yengo, Loïc; Yoon, Kyungheon; Yu, Canqing; Yuan, Jian-Min; Yusuf, Salim; Zhang, Liang; Zheng, Wei; Raffel, Leslie J.; Igase, Michiya; Ipp, Eli; Redline, Susan; Cho, Yoon Shin; Lind, Lars; Province, Michael A.; Hanis, Craig L.; Peyser, Patricia A.; Ingelsson, Erik; Zonderman, Alan B.; Psaty, Bruce M.; Wang, Ya-Xing; Rotimi, Charles N.; Becker, Diane M.; Matsuda, Fumihiko; Liu, Yongmei; Zeggini, Eleftheria; Yokota, Mitsuhiro; Rich, Stephen S.; Kooperberg, Charles; Pankow, James S.; Engert, James C.; Chen, Yii-Der Ida; Froguel, Philippe; Wilson, James G.; Sheu, Wayne H. H.; Kardia, Sharon L. R.; Wu, Jer-Yuarn; Hayes, M. Geoffrey; Ma, Ronald C. W.; Wong, Tien-Yin; Groop, Leif; Mook-Kanamori, Dennis O.; Chandak, Giriraj R.; Collins, Francis S.; Bharadwaj, Dwaipayan; Paré, Guillaume; Sale, Michèle M.; Ahsan, Habibul; Motala, Ayesha A.; Shu, Xiao-Ou; Park, Kyong-Soo; Jukema, J. Wouter; Cruz, Miguel; McKean-Cowdin, Roberta; Grallert, Harald; Cheng, Ching-Yu; Bottinger, Erwin P.; Dehghan, Abbas; Tai, E-Shyong; Dupuis, Josée; Kato, Norihiro; Laakso, Markku; Köttgen, Anna; Koh, Woon-Puay; Palmer, Colin N. A.; Liu, Simin; Abecasis, Goncalo; Kooner, Jaspal S.; Loos, Ruth J. F.; North, Kari E.; Haiman, Christopher A.; Florez, Jose C.; Saleheen, Danish; Hansen, Torben; Pedersen, Oluf; Mägi, Reedik; Langenberg, Claudia; Wareham, Nicholas J.; Maeda, Shiro; Kadowaki, Takashi; Lee, Juyoung; Millwood, Iona Y.; Walters, Robin G.; Stefansson, Kari; Myers, Simon R.; Ferrer, Jorge; Gaulton, Kyle J.; Meigs, James B.; Mohlke, Karen L.; Gloyn, Anna L.; Bowden, Donald W.; Below, Jennifer E.; Chambers, John C.; Sim, Xueling; Boehnke, Michael; Rotter, Jerome I.; McCarthy, Mark I.; Morris, Andrew P.
Source
Nature Genetics; 20220101, Issue: Preprints p1-13, 13p
Subject
Language
ISSN
10614036; 15461718
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.