Multi-Ancestry Genetic Study of Type 2 Diabetes Highlights the Power of Diverse Populations for Discovery and Translation

Citation

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, et al. (2022). Multi-Ancestry Genetic Study of Type 2 Diabetes Highlights the Power of Diverse Populations for Discovery and Translation. Nature Genetics, 54(5), 560-572. PMCID: PMC9179018

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.

URL

http://dx.doi.org/10.1038/s41588-022-01058-3

Reference Type

Journal Article

Year Published

2022

Journal Title

Nature Genetics

Author(s)

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 Y.
Chen, Chien-Hsiun
Raffield, Laura M.
Lecoeur, Cécile
Prins, Bram Peter
Nicolas, Aude
Yanek, Lisa R.
Chen, Guanjie
Jensen, Richard A.
Tajuddin, Salman M.
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 A.
Aguilar-Salinas, Carlos A.
Akiyama, Masato
Anand, Sonia S.
Bertoni, Alain G.
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 M.
Gerstein, Hertzel C.
Giedraitis, Vilmantas
González-Villalpando, Clicerio
González-Villalpando, Maria E.
Goodarzi, Mark O.
Gordon-Larsen, Penny
Gorkin, David
Gross, Myron D.
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 A.
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. R.
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 A.
Smith, Jennifer A.
So, Wing Yee
Stan
č
áková, 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 S.
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.
Kardia, Sharon L. R.
Wu, Jer-Yuarn
Hayes, M. Geoffrey
Ma, Ronald C. W.
Wong, Tien-Yin
Groop, Leif C.
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 R.
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.

Article Type

Regular

PMCID

PMC9179018

Data Set/Study

Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium

Race/Ethnicity

African Ancestry
East Asian Ancestry
European Ancestry
Hispanic Ancestry
South Asian Ancestry

ORCiD

Adair - 0000-0002-3670-8073
Howard, AG - 0000-0003-0837-8166
Du - 0000-0003-1156-0866
Gordon-Larsen - 0000-0001-5322-4188
Graff - 0000-0001-6380-1735