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

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

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.

authors

  • Mahajan, Anubha
  • Spracklen, Cassandra N
  • Zhang, Weihua
  • Ng, Maggie CY
  • 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 JY
  • Tam, Claudia HT
  • 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
  • Bertoni, Alain
  • Bian, Zheng
  • Bork-Jensen, Jette
  • Brandslund, Ivan
  • Brody, Jennifer A
  • Brummett, Chad M
  • Buchanan, Thomas A
  • Canouil, Mickaël
  • Chan, Juliana CN
  • 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 Chaim
  • 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
  • Rüeger, Sina
  • della Briotta Parolo, Pietro
  • Joo, Yoonjung Yoonie
  • Hayes, M Geoffrey
  • 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 HH
  • Kardia, Sharon LR
  • Wu, Jer-Yuarn
  • Hayes, M Geoffrey
  • Ma, Ronald CW
  • Wong, Tien-Yin
  • Groop, Leif
  • Mook-Kanamori, Dennis O
  • Chandak, Giriraj R
  • Collins, Francis S
  • Bharadwaj, Dwaipayan
  • Pare, 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 NA
  • Liu, Simin
  • Abecasis, Goncalo
  • Kooner, Jaspal S
  • Loos, Ruth JF
  • 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

publication date

  • May 2022