Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation-Reference-Cited by-同舟云学术

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

Published:2020-09-23 Issue: Volume: Page:
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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^ORCID,Miguel-Escalada Irene,Briotta Parolo Pietro della,Lin Kuang,Bragg Fiona,Preuss Michael H,Takeuchi Fumihiko^ORCID,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^ORCID,Chen Chien-Hsiun,Raffield Laura M^ORCID,Lecoeur Cécile,Maruthur Nisa M,Prins Bram Peter,Nicolas Aude,Yanek Lisa R,Chen Guanjie,Jensen Richard A,Tajuddin Salman,Kabagambe Edmond,An Ping,Xiang Anny H,Choi Hyeok Sun,Cade Brian E,Tan Jingyi,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^ORCID,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^ORCID,Fischer Krista,Floyd James S,Ford Ian,Fornage Myriam^ORCID,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^ORCID,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^ORCID,Metspalu Andres,Morris Andrew D,Nadkarni Girish N.,Nadler Jerry L,Nalls Michael A,Nayak Uma,Ntalla Ioanna,Okada Yukinori^ORCID,Orozco Lorena,Patel Sanjay R,Pereira Mark A,Peters Annette,Pirie Fraser J,Porneala Bianca,Prasad Gauri,Preissl Sebastian^ORCID,Rasmussen-Torvik Laura J^ORCID,Reiner Alexander P,Roden Michael,Rohde Rebecca,Roll Katheryn,Sabanayagam Charumathi,Sander Maike^ORCID,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^ORCID,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^ORCID,Wacher-Rodarte Niels,Wheeler Ellie,Whitsel Eric A,Wickremasinghe Ananda R,van Dijk Konstantin 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^ORCID,FinnGen ,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^ORCID,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^ORCID,Paré Guillaume^ORCID,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 Josee,Kato Norihiro,Laakso Markku,Köttgen Anna,Koh Woon-Puay,Palmer Colin NA,Liu Simin^ORCID,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^ORCID,Wareham Nicholas J,Maeda Shiro,Kadowaki Takashi,Lee Juyoung,Millwood Iona Y,Walters Robin G^ORCID,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^ORCID,Morris Andrew P

Abstract

ABSTRACTWe assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5×10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5×10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved 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 foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

Publisher

Cold Spring Harbor Laboratory

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