Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Anubha Mahajan; Min Jin Go; Weihua Zhang; Jennifer E. Below; Kyle J. Gaulton; Teresa Ferreira; Momoko Horikoshi; Andrew D. Johnson; Maggie C Y Ng; Inga Prokopenko; Danish Saleheen; Xu Wang; Eleftheria Zeggini; Goncalo R. Abecasis; Linda S. Adair; Peter Almgren; Mustafa Atalay; Tin Aung; Damiano Baldassarre; Beverley Balkau; Yuqian Bao; Anthony H. Barnett; Ines Barroso; Abdul Basit; Latonya F. Been; John Beilby; Graeme I. Bell; Rafn Benediktsson; Richard N. Bergman; Bernhard OBoehm; Eric Boerwinkle; Lori L. Bonnycastle; Noël Burtt; Qiuyin Cai; Harry Campbell; Jason Carey; Stephane Cauchi; Mark Caulfield; Juliana C N Chan; Li Ching Chang; Tien Jyun Chang; Yi Cheng Chang; Guillaume Charpentier; Chien Hsiun Chen; Han Chen; Yuan Tsong Chen; Kee Seng Chia; Manickam Chidambaram; Peter S. Chines; Nam H. Cho; Young Min Cho; Lee Ming Chuang; Francis S. Collins; Marilyn C. Cornelis; David J. Couper; Andrew T. Crenshaw; Rob M. Van Dam; John Danesh; Debashish Das; Ulf De Faire; George Dedoussis; Panos Deloukas; Antigone S. Dimas; Christian Dina; Alex S F Doney; Peter J. Donnelly; Mozhgan Dorkhan; Cornelia Van Duijn; Josée Dupuis; Sarah Edkins; Paul Elliott; Valur Emilsson; Raimund Erbel; Johan G. Eriksson; Jorge Escobedo; Tonu Esko; Elodie Eury; Jose C. Florez; Pierre Fontanillas; Nita G. Forouhi; Tom Forsen; Caroline Fox; Ross M. Fraser; Timothy M. Frayling; Philippe Froguel; Philippe Frossard; Yutang Gao; Karl Gertow; Christian Gieger; Bruna Gigante; Harald Grallert; George B. Grant; Leif C. Groop; Christopher J. Groves; Elin Grundberg; Candace Guiducci; Anders Hamsten; Bok Ghee Han; Kazuo Hara; Neelam Hassanali; Andrew T. Hattersley; Caroline Hayward; Asa K. Hedman; Christian Herder; Albert Hofman; Oddgeir L. Holmen; Kees Hovingh; Astradur B. Hreidarsson; Cheng Hu; Frank B. Hu; Jennie Hui; Steve E. Humphries; Sarah E. Hunt; David J. Hunter; Kristian Hveem; Zafar I. Hydrie; Hiroshi Ikegami; Thomas Illig; Erik Ingelsson; Muhammed Islam; Bo Isomaa; Anne U. Jackson; Tazeen Jafar; Alan James; Weiping Jia; Karl Heinz Jöckel; Anna Jonsson; Jeremy B M Jowett; Takashi Kadowaki; Hyun Min Kang; Stavroula Kanoni; Wen Hong L Kao; Sekar Kathiresan; Norihiro Kato; Prasad Katulanda; Sirkka M. Keinanen-Kiukaanniemi; Ann M. Kelly; Hassan Khan; Kay Tee Khaw; Chiea Chuen Khor; Hyung Lae Kim; Sangsoo Kim; Young Jin Kim; Leena Kinnunen; Norman Klopp; Augustine Kong; Eeva Korpi-Hyövälti; Sudhir Kowlessur; Peter Kraft; Jasmina Kravic; Malene M. Kristensen; S. Krithika; Ashish Kumar; Jesus Kumate; Johanna Kuusisto; Soo Heon Kwak; Markku Laakso; Vasiliki Lagou; Timo A. Lakka; Claudia Langenberg; Cordelia Langford; Robert Lawrence; Karin Leander; Jen Mai Lee; Nanette R. Lee; Man Li; Xinzhong Li; Yun Li; Junbin Liang; Samuel Liju; Wei Yen Lim; Lars Lind; Cecilia M. Lindgren; Eero Lindholm; Ching Ti Liu; Jian Jun Liu; Stéphane Lobbens; Jirong Long; Ruth J F Loos; Wei Lu; Jianan Luan; Valeriya Lyssenko; Ronald C. WMa; Shiro Maeda; Reedik Mägi; Satu Männistö; David R. Matthews; James B. Meigs; Olle Melander; Andres Metspalu; Julia Meyer; Ghazala Mirza; Evelin Mihailov; Susanne Moebus; Viswanathan Mohan; Karen L. Mohlke; Andrew D. Morris; Thomas WMühleisen; Martina Müller-Nurasyid; Bill Musk; Jiro Nakamura; Eitaro Nakashima; Pau Navarro; Peng Keat Ng; Alexandra C. Nica; Peter M. Nilsson; Inger Njølstad; Markus M. Nöthen; Keizo Ohnaka; Twee Hee Ong; Katharine R. Owen; Colin N A Palmer; James S. Pankow; Kyong Soo Park; Melissa Parkin; Sonali Pechlivanis; Nancy L. Pedersen; Leena Peltonen; John R B Perry; Annette Peters; Janani M. Pinidiyapathirage; Carl G P Platou; Simon Potter; Jackie F. Price; Lu Qi; Venkatesan Radha; Loukianos Rallidis; Asif Rasheed; Wolfgang Rathmann; Rainer Rauramaa; Soumya Raychaudhuri; N. William Rayner; Simon D. Rees; Emil Rehnberg; Samuli Ripatti; Neil Robertson; Michael Roden; Elizabeth J. Rossin; Igor Rudan; Denis Rybin; Timo E. Saaristo; Veikko Salomaa; Juha Saltevo; Maria Samuel; Dharambir KSanghera; Jouko Saramies; James Scott; Laura J. Scott; Robert A. Scott; Ayellet V. Segrè; Joban Sehmi; Bengt Sennblad; Nabi Shah; Sonia Shah; A. Samad Shera; Xiao Ou Shu; Alan R. Shuldiner; Gunnar Sigurosson; Eric Sijbrands; Angela Silveira; Xueling Sim; Suthesh Sivapalaratnam; Kerrin S. Small; Wing Yee So; Alena Stančáková; Kari Stefansson; Gerald Steinbach; Valgerdur Steinthorsdottir; Kathleen Stirrups; Rona J. Strawbridge; Heather M. Stringham; Qi Sun; Chen Suo; Ann Christine Syvänen; Ryoichi Takayanagi; Fumihiko Takeuchi; Wan Ting Tay; Tanya M. Teslovich; Barbara Thorand; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Emmi Tikkanen; Joseph Trakalo; Elena Tremoli; Mieke D. Trip; Fuu Jen Tsai; Tiinamaija Tuomi; Jaakko Tuomilehto; Andre G. Uitterlinden; Adan Valladares-Salgado; Sailaja Vedantam; Fabrizio Veglia; Benjamin F. Voight; Congrong Wang; Nicholas J. Wareham; Roman Wennauer; Ananda R. Wickremasinghe; Tom Wilsgaard; James F. Wilson; Steven Wiltshire; Wendy Winckler; Tien Yin Wong; Andrew R. Wood; Jer Yuarn Wu; Ying Wu; Ken Yamamoto; Toshimasa Yamauchi; Mingyu Yang; Loic Yengo; Mitsuhiro Yokota; Robin Young; Delilah Zabaneh; Fan Zhang; Rong Zhang; Wei Zheng; Paul Z. Zimmet; David Altshuler; Donald W. Bowden; Yoon Shin Cho; Nancy J. Cox; Miguel Cruz; Craig L. Hanis; Jaspal Kooner; Jong Young Lee; Mark Seielstad; Yik Ying Teo; Michael Boehnke; Esteban J. Parra; John C. Chambers; E. Shyong Tai; Mark I. McCarthy; Andrew P. Morris

doi:10.1038/ng.2897

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Anubha Mahajan
, Min Jin Go
, Weihua Zhang
, Jennifer E. Below
, Kyle J. Gaulton
, Teresa Ferreira
, Momoko Horikoshi
, Andrew D. Johnson
, Maggie C Y Ng
, Inga Prokopenko
, Danish Saleheen
, Xu Wang
, Eleftheria Zeggini
, Goncalo R. Abecasis
, Linda S. Adair
, Peter Almgren
, Mustafa Atalay
, Tin Aung
, Damiano Baldassarre
, Beverley Balkau

Yuqian Bao, Anthony H. Barnett, Ines Barroso, Abdul Basit, Latonya F. Been, John Beilby, Graeme I. Bell, Rafn Benediktsson, Richard N. Bergman, Bernhard OBoehm, Eric Boerwinkle, Lori L. Bonnycastle, Noël Burtt, Qiuyin Cai, Harry Campbell, Jason Carey, Stephane Cauchi, Mark Caulfield, Juliana C N Chan, Li Ching Chang, Tien Jyun Chang, Yi Cheng Chang, Guillaume Charpentier, Chien Hsiun Chen, Han Chen, Yuan Tsong Chen, Kee Seng Chia, Manickam Chidambaram, Peter S. Chines, Nam H. Cho, Young Min Cho, Lee Ming Chuang, Francis S. Collins, Marilyn C. Cornelis, David J. Couper, Andrew T. Crenshaw, Rob M. Van Dam, John Danesh, Debashish Das, Ulf De Faire, George Dedoussis, Panos Deloukas, Antigone S. Dimas, Christian Dina, Alex S F Doney, Peter J. Donnelly, Mozhgan Dorkhan, Cornelia Van Duijn, Josée Dupuis, Sarah Edkins, Paul Elliott, Valur Emilsson, Raimund Erbel, Johan G. Eriksson, Jorge Escobedo, Tonu Esko, Elodie Eury, Jose C. Florez, Pierre Fontanillas, Nita G. Forouhi, Tom Forsen, Caroline Fox, Ross M. Fraser, Timothy M. Frayling, Philippe Froguel, Philippe Frossard, Yutang Gao, Karl Gertow, Christian Gieger, Bruna Gigante, Harald Grallert, George B. Grant, Leif C. Groop, Christopher J. Groves, Elin Grundberg, Candace Guiducci, Anders Hamsten, Bok Ghee Han, Kazuo Hara, Neelam Hassanali, Andrew T. Hattersley, Caroline Hayward, Asa K. Hedman, Christian Herder, Albert Hofman, Oddgeir L. Holmen, Kees Hovingh, Astradur B. Hreidarsson, Cheng Hu, Frank B. Hu, Jennie Hui, Steve E. Humphries, Sarah E. Hunt, David J. Hunter, Kristian Hveem, Zafar I. Hydrie, Hiroshi Ikegami, Thomas Illig, Erik Ingelsson, Muhammed Islam, Bo Isomaa, Anne U. Jackson, Tazeen Jafar, Alan James, Weiping Jia, Karl Heinz Jöckel, Anna Jonsson, Jeremy B M Jowett, Takashi Kadowaki, Hyun Min Kang, Stavroula Kanoni, Wen Hong L Kao, Sekar Kathiresan, Norihiro Kato, Prasad Katulanda, Sirkka M. Keinanen-Kiukaanniemi, Ann M. Kelly, Hassan Khan, Kay Tee Khaw, Chiea Chuen Khor, Hyung Lae Kim, Sangsoo Kim, Young Jin Kim, Leena Kinnunen, Norman Klopp, Augustine Kong, Eeva Korpi-Hyövälti, Sudhir Kowlessur, Peter Kraft, Jasmina Kravic, Malene M. Kristensen, S. Krithika, Ashish Kumar, Jesus Kumate, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Vasiliki Lagou, Timo A. Lakka, Claudia Langenberg, Cordelia Langford, Robert Lawrence, Karin Leander, Jen Mai Lee, Nanette R. Lee, Man Li, Xinzhong Li, Yun Li, Junbin Liang, Samuel Liju, Wei Yen Lim, Lars Lind, Cecilia M. Lindgren, Eero Lindholm, Ching Ti Liu, Jian Jun Liu, Stéphane Lobbens, Jirong Long, Ruth J F Loos, Wei Lu, Jianan Luan, Valeriya Lyssenko, Ronald C. WMa, Shiro Maeda, Reedik Mägi, Satu Männistö, David R. Matthews, James B. Meigs, Olle Melander, Andres Metspalu, Julia Meyer, Ghazala Mirza, Evelin Mihailov, Susanne Moebus, Viswanathan Mohan, Karen L. Mohlke, Andrew D. Morris, Thomas WMühleisen, Martina Müller-Nurasyid, Bill Musk, Jiro Nakamura, Eitaro Nakashima, Pau Navarro, Peng Keat Ng, Alexandra C. Nica, Peter M. Nilsson, Inger Njølstad, Markus M. Nöthen, Keizo Ohnaka, Twee Hee Ong, Katharine R. Owen, Colin N A Palmer, James S. Pankow, Kyong Soo Park, Melissa Parkin, Sonali Pechlivanis, Nancy L. Pedersen, Leena Peltonen, John R B Perry, Annette Peters, Janani M. Pinidiyapathirage, Carl G P Platou, Simon Potter, Jackie F. Price, Lu Qi, Venkatesan Radha, Loukianos Rallidis, Asif Rasheed, Wolfgang Rathmann, Rainer Rauramaa, Soumya Raychaudhuri, N. William Rayner, Simon D. Rees, Emil Rehnberg, Samuli Ripatti, Neil Robertson, Michael Roden, Elizabeth J. Rossin, Igor Rudan, Denis Rybin, Timo E. Saaristo, Veikko Salomaa, Juha Saltevo, Maria Samuel, Dharambir KSanghera, Jouko Saramies, James Scott, Laura J. Scott, Robert A. Scott, Ayellet V. Segrè, Joban Sehmi, Bengt Sennblad, Nabi Shah, Sonia Shah, A. Samad Shera, Xiao Ou Shu, Alan R. Shuldiner, Gunnar Sigurosson, Eric Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S. Small, Wing Yee So, Alena Stančáková, Kari Stefansson, Gerald Steinbach, Valgerdur Steinthorsdottir, Kathleen Stirrups, Rona J. Strawbridge, Heather M. Stringham, Qi Sun, Chen Suo, Ann Christine Syvänen, Ryoichi Takayanagi, Fumihiko Takeuchi, Wan Ting Tay, Tanya M. Teslovich, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Emmi Tikkanen, Joseph Trakalo, Elena Tremoli, Mieke D. Trip, Fuu Jen Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Andre G. Uitterlinden, Adan Valladares-Salgado, Sailaja Vedantam, Fabrizio Veglia, Benjamin F. Voight, Congrong Wang, Nicholas J. Wareham, Roman Wennauer, Ananda R. Wickremasinghe, Tom Wilsgaard, James F. Wilson, Steven Wiltshire, Wendy Winckler, Tien Yin Wong, Andrew R. Wood, Jer Yuarn Wu, Ying Wu, Ken Yamamoto, Toshimasa Yamauchi, Mingyu Yang, Loic Yengo, Mitsuhiro Yokota, Robin Young, Delilah Zabaneh, Fan Zhang, Rong Zhang, Wei Zheng, Paul Z. Zimmet, David Altshuler, Donald W. Bowden, Yoon Shin Cho, Nancy J. Cox, Miguel Cruz, Craig L. Hanis, Jaspal Kooner, Jong Young Lee, Mark Seielstad, Yik Ying Teo, Michael Boehnke, Esteban J. Parra, John C. Chambers, E. Shyong Tai, Mark I. McCarthy, Andrew P. Morris

Epidemiology & Community Health

Research output: Contribution to journal › Article › peer-review

890 Scopus citations

Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Original language	English (US)
Pages (from-to)	234-244
Number of pages	11
Journal	Nature Genetics
Volume	46
Issue number	3
DOIs	https://doi.org/10.1038/ng.2897
State	Published - Mar 2014

Bibliographical note

Funding Information:
Funding for the research undertaken in this study has been received from the following: the Canadian Institutes of Health Research; the European Commission (ENGAGE FP7 HEALTH-F4-2007-201413); the Medical Research Council UK (G0601261); the Mexico Convocatoria (SSA/IMMS/ISSSTE-CONACYT 2012-2, clave 150352, IMSS R-2011-785-018 and CONACYT Salud-2007-C01-71068); the US National Institutes of Health (DK062370, HG000376, DK085584, DK085545, DK073541 and DK085501); and the Wellcome Trust (WT098017, WT090532, WT090367, WT098381, WT081682 and WT085475). We acknowledge the many colleagues who contributed to collection and phenotypic characterization of the clinical samples and the genotyping and analysis of the GWAS data, full details of which are provided in the contributing consortia papers5,11,13,15. We also thank those individuals who agreed to participate in this study.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Publisher link

10.1038/ng.2897

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Mahajan, A., Go, M. J., Zhang, W., Below, J. E., Gaulton, K. J., Ferreira, T., Horikoshi, M., Johnson, A. D., Ng, M. C. Y., Prokopenko, I., Saleheen, D., Wang, X., Zeggini, E., Abecasis, G. R., Adair, L. S., Almgren, P., Atalay, M., Aung, T., Baldassarre, D., ... Morris, A. P. (2014). Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nature Genetics, 46(3), 234-244. https://doi.org/10.1038/ng.2897

Mahajan, A, Go, MJ, Zhang, W, Below, JE, Gaulton, KJ, Ferreira, T, Horikoshi, M, Johnson, AD, Ng, MCY, Prokopenko, I, Saleheen, D, Wang, X, Zeggini, E, Abecasis, GR, Adair, LS, Almgren, P, Atalay, M, Aung, T, Baldassarre, D, Balkau, B, Bao, Y, Barnett, AH, Barroso, I, Basit, A, Been, LF, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, OBoehm, B, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, Q, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, LC, Chang, TJ, Chang, YC, Charpentier, G, Chen, CH, Chen, H, Chen, YT, Chia, KS, Chidambaram, M, Chines, PS, Cho, NH, Cho, YM, Chuang, LM, Collins, FS, Cornelis, MC, Couper, DJ, Crenshaw, AT, Van Dam, RM, Danesh, J, Das, D, De Faire, U, Dedoussis, G, Deloukas, P, Dimas, AS, Dina, C, Doney, ASF, Donnelly, PJ, Dorkhan, M, Van Duijn, C, Dupuis, J, Edkins, S, Elliott, P, Emilsson, V, Erbel, R, Eriksson, JG, Escobedo, J, Esko, T, Eury, E, Florez, JC, Fontanillas, P, Forouhi, NG, Forsen, T, Fox, C, Fraser, RM, Frayling, TM, Froguel, P, Frossard, P, Gao, Y, Gertow, K, Gieger, C, Gigante, B, Grallert, H, Grant, GB, Groop, LC, Groves, CJ, Grundberg, E, Guiducci, C, Hamsten, A, Han, BG, Hara, K, Hassanali, N, Hattersley, AT, Hayward, C, Hedman, AK, Herder, C, Hofman, A, Holmen, OL, Hovingh, K, Hreidarsson, AB, Hu, C, Hu, FB, Hui, J, Humphries, SE, Hunt, SE, Hunter, DJ, Hveem, K, Hydrie, ZI, Ikegami, H, Illig, T, Ingelsson, E, Islam, M, Isomaa, B, Jackson, AU, Jafar, T, James, A, Jia, W, Jöckel, KH, Jonsson, A, Jowett, JBM, Kadowaki, T, Kang, HM, Kanoni, S, Kao, WHL, Kathiresan, S, Kato, N, Katulanda, P, Keinanen-Kiukaanniemi, SM, Kelly, AM, Khan, H, Khaw, KT, Khor, CC, Kim, HL, Kim, S, Kim, YJ, Kinnunen, L, Klopp, N, Kong, A, Korpi-Hyövälti, E, Kowlessur, S, Kraft, P, Kravic, J, Kristensen, MM, Krithika, S, Kumar, A, Kumate, J, Kuusisto, J, Kwak, SH, Laakso, M, Lagou, V, Lakka, TA, Langenberg, C, Langford, C, Lawrence, R, Leander, K, Lee, JM, Lee, NR, Li, M, Li, X, Li, Y, Liang, J, Liju, S, Lim, WY, Lind, L, Lindgren, CM, Lindholm, E, Liu, CT, Liu, JJ, Lobbens, S, Long, J, Loos, RJF, Lu, W, Luan, J, Lyssenko, V, WMa, RC, Maeda, S, Mägi, R, Männistö, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, WMühleisen, T, Müller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Ng, PK, Nica, AC, Nilsson, PM, Njølstad, I, Nöthen, MM, Ohnaka, K, Ong, TH, Owen, KR, Palmer, CNA, Pankow, JS, Park, KS, Parkin, M, Pechlivanis, S, Pedersen, NL, Peltonen, L, Perry, JRB, Peters, A, Pinidiyapathirage, JM, Platou, CGP, Potter, S, Price, JF, Qi, L, Radha, V, Rallidis, L, Rasheed, A, Rathmann, W, Rauramaa, R, Raychaudhuri, S, Rayner, NW, Rees, SD, Rehnberg, E, Ripatti, S, Robertson, N, Roden, M, Rossin, EJ, Rudan, I, Rybin, D, Saaristo, TE, Salomaa, V, Saltevo, J, Samuel, M, KSanghera, D, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segrè, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurosson, G, Sijbrands, E, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stančáková, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvänen, AC, Takayanagi, R, Takeuchi, F, Tay, WT, Teslovich, TM, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Trakalo, J, Tremoli, E, Trip, MD, Tsai, FJ, Tuomi, T, Tuomilehto, J, Uitterlinden, AG, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, C, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, JY, Wu, Y, Yamamoto, K, Yamauchi, T, Yang, M, Yengo, L, Yokota, M, Young, R, Zabaneh, D, Zhang, F, Zhang, R, Zheng, W, Zimmet, PZ, Altshuler, D, Bowden, DW, Cho, YS, Cox, NJ, Cruz, M, Hanis, CL, Kooner, J, Lee, JY, Seielstad, M, Teo, YY, Boehnke, M, Parra, EJ, Chambers, JC, Tai, ES, McCarthy, MI & Morris, AP 2014, 'Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility', Nature Genetics, vol. 46, no. 3, pp. 234-244. https://doi.org/10.1038/ng.2897

@article{a8cec1474fd7441dbae341e29fe8fe22,

title = "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility",

abstract = "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.",

author = "Anubha Mahajan and Go, \{Min Jin\} and Weihua Zhang and Below, \{Jennifer E.\} and Gaulton, \{Kyle J.\} and Teresa Ferreira and Momoko Horikoshi and Johnson, \{Andrew D.\} and Ng, \{Maggie C Y\} and Inga Prokopenko and Danish Saleheen and Xu Wang and Eleftheria Zeggini and Abecasis, \{Goncalo R.\} and Adair, \{Linda S.\} and Peter Almgren and Mustafa Atalay and Tin Aung and Damiano Baldassarre and Beverley Balkau and Yuqian Bao and Barnett, \{Anthony H.\} and Ines Barroso and Abdul Basit and Been, \{Latonya F.\} and John Beilby and Bell, \{Graeme I.\} and Rafn Benediktsson and Bergman, \{Richard N.\} and Bernhard OBoehm and Eric Boerwinkle and Bonnycastle, \{Lori L.\} and No{\"e}l Burtt and Qiuyin Cai and Harry Campbell and Jason Carey and Stephane Cauchi and Mark Caulfield and Chan, \{Juliana C N\} and Chang, \{Li Ching\} and Chang, \{Tien Jyun\} and Chang, \{Yi Cheng\} and Guillaume Charpentier and Chen, \{Chien Hsiun\} and Han Chen and Chen, \{Yuan Tsong\} and Chia, \{Kee Seng\} and Manickam Chidambaram and Chines, \{Peter S.\} and Cho, \{Nam H.\} and Cho, \{Young Min\} and Chuang, \{Lee Ming\} and Collins, \{Francis S.\} and Cornelis, \{Marilyn C.\} and Couper, \{David J.\} and Crenshaw, \{Andrew T.\} and \{Van Dam\}, \{Rob M.\} and John Danesh and Debashish Das and \{De Faire\}, Ulf and George Dedoussis and Panos Deloukas and Dimas, \{Antigone S.\} and Christian Dina and Doney, \{Alex S F\} and Donnelly, \{Peter J.\} and Mozhgan Dorkhan and \{Van Duijn\}, Cornelia and Jos{\'e}e Dupuis and Sarah Edkins and Paul Elliott and Valur Emilsson and Raimund Erbel and Eriksson, \{Johan G.\} and Jorge Escobedo and Tonu Esko and Elodie Eury and Florez, \{Jose C.\} and Pierre Fontanillas and Forouhi, \{Nita G.\} and Tom Forsen and Caroline Fox and Fraser, \{Ross M.\} and Frayling, \{Timothy M.\} and Philippe Froguel and Philippe Frossard and Yutang Gao and Karl Gertow and Christian Gieger and Bruna Gigante and Harald Grallert and Grant, \{George B.\} and Groop, \{Leif C.\} and Groves, \{Christopher J.\} and Elin Grundberg and Candace Guiducci and Anders Hamsten and Han, \{Bok Ghee\} and Kazuo Hara and Neelam Hassanali and Hattersley, \{Andrew T.\} and Caroline Hayward and Hedman, \{Asa K.\} and Christian Herder and Albert Hofman and Holmen, \{Oddgeir L.\} and Kees Hovingh and Hreidarsson, \{Astradur B.\} and Cheng Hu and Hu, \{Frank B.\} and Jennie Hui and Humphries, \{Steve E.\} and Hunt, \{Sarah E.\} and Hunter, \{David J.\} and Kristian Hveem and Hydrie, \{Zafar I.\} and Hiroshi Ikegami and Thomas Illig and Erik Ingelsson and Muhammed Islam and Bo Isomaa and Jackson, \{Anne U.\} and Tazeen Jafar and Alan James and Weiping Jia and J{\"o}ckel, \{Karl Heinz\} and Anna Jonsson and Jowett, \{Jeremy B M\} and Takashi Kadowaki and Kang, \{Hyun Min\} and Stavroula Kanoni and Kao, \{Wen Hong L\} and Sekar Kathiresan and Norihiro Kato and Prasad Katulanda and Keinanen-Kiukaanniemi, \{Sirkka M.\} and Kelly, \{Ann M.\} and Hassan Khan and Khaw, \{Kay Tee\} and Khor, \{Chiea Chuen\} and Kim, \{Hyung Lae\} and Sangsoo Kim and Kim, \{Young Jin\} and Leena Kinnunen and Norman Klopp and Augustine Kong and Eeva Korpi-Hy{\"o}v{\"a}lti and Sudhir Kowlessur and Peter Kraft and Jasmina Kravic and Kristensen, \{Malene M.\} and S. Krithika and Ashish Kumar and Jesus Kumate and Johanna Kuusisto and Kwak, \{Soo Heon\} and Markku Laakso and Vasiliki Lagou and Lakka, \{Timo A.\} and Claudia Langenberg and Cordelia Langford and Robert Lawrence and Karin Leander and Lee, \{Jen Mai\} and Lee, \{Nanette R.\} and Man Li and Xinzhong Li and Yun Li and Junbin Liang and Samuel Liju and Lim, \{Wei Yen\} and Lars Lind and Lindgren, \{Cecilia M.\} and Eero Lindholm and Liu, \{Ching Ti\} and Liu, \{Jian Jun\} and St{\'e}phane Lobbens and Jirong Long and Loos, \{Ruth J F\} and Wei Lu and Jianan Luan and Valeriya Lyssenko and WMa, \{Ronald C.\} and Shiro Maeda and Reedik M{\"a}gi and Satu M{\"a}nnist{\"o} and Matthews, \{David R.\} and Meigs, \{James B.\} and Olle Melander and Andres Metspalu and Julia Meyer and Ghazala Mirza and Evelin Mihailov and Susanne Moebus and Viswanathan Mohan and Mohlke, \{Karen L.\} and Morris, \{Andrew D.\} and Thomas WM{\"u}hleisen and Martina M{\"u}ller-Nurasyid and Bill Musk and Jiro Nakamura and Eitaro Nakashima and Pau Navarro and Ng, \{Peng Keat\} and Nica, \{Alexandra C.\} and Nilsson, \{Peter M.\} and Inger Nj{\o}lstad and N{\"o}then, \{Markus M.\} and Keizo Ohnaka and Ong, \{Twee Hee\} and Owen, \{Katharine R.\} and Palmer, \{Colin N A\} and Pankow, \{James S.\} and Park, \{Kyong Soo\} and Melissa Parkin and Sonali Pechlivanis and Pedersen, \{Nancy L.\} and Leena Peltonen and Perry, \{John R B\} and Annette Peters and Pinidiyapathirage, \{Janani M.\} and Platou, \{Carl G P\} and Simon Potter and Price, \{Jackie F.\} and Lu Qi and Venkatesan Radha and Loukianos Rallidis and Asif Rasheed and Wolfgang Rathmann and Rainer Rauramaa and Soumya Raychaudhuri and Rayner, \{N. William\} and Rees, \{Simon D.\} and Emil Rehnberg and Samuli Ripatti and Neil Robertson and Michael Roden and Rossin, \{Elizabeth J.\} and Igor Rudan and Denis Rybin and Saaristo, \{Timo E.\} and Veikko Salomaa and Juha Saltevo and Maria Samuel and Dharambir KSanghera and Jouko Saramies and James Scott and Scott, \{Laura J.\} and Scott, \{Robert A.\} and Segr{\`e}, \{Ayellet V.\} and Joban Sehmi and Bengt Sennblad and Nabi Shah and Sonia Shah and Shera, \{A. Samad\} and Shu, \{Xiao Ou\} and Shuldiner, \{Alan R.\} and Gunnar Sigurosson and Eric Sijbrands and Angela Silveira and Xueling Sim and Suthesh Sivapalaratnam and Small, \{Kerrin S.\} and So, \{Wing Yee\} and Alena Stan{\v c}{\'a}kov{\'a} and Kari Stefansson and Gerald Steinbach and Valgerdur Steinthorsdottir and Kathleen Stirrups and Strawbridge, \{Rona J.\} and Stringham, \{Heather M.\} and Qi Sun and Chen Suo and Syv{\"a}nen, \{Ann Christine\} and Ryoichi Takayanagi and Fumihiko Takeuchi and Tay, \{Wan Ting\} and Teslovich, \{Tanya M.\} and Barbara Thorand and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Emmi Tikkanen and Joseph Trakalo and Elena Tremoli and Trip, \{Mieke D.\} and Tsai, \{Fuu Jen\} and Tiinamaija Tuomi and Jaakko Tuomilehto and Uitterlinden, \{Andre G.\} and Adan Valladares-Salgado and Sailaja Vedantam and Fabrizio Veglia and Voight, \{Benjamin F.\} and Congrong Wang and Wareham, \{Nicholas J.\} and Roman Wennauer and Wickremasinghe, \{Ananda R.\} and Tom Wilsgaard and Wilson, \{James F.\} and Steven Wiltshire and Wendy Winckler and Wong, \{Tien Yin\} and Wood, \{Andrew R.\} and Wu, \{Jer Yuarn\} and Ying Wu and Ken Yamamoto and Toshimasa Yamauchi and Mingyu Yang and Loic Yengo and Mitsuhiro Yokota and Robin Young and Delilah Zabaneh and Fan Zhang and Rong Zhang and Wei Zheng and Zimmet, \{Paul Z.\} and David Altshuler and Bowden, \{Donald W.\} and Cho, \{Yoon Shin\} and Cox, \{Nancy J.\} and Miguel Cruz and Hanis, \{Craig L.\} and Jaspal Kooner and Lee, \{Jong Young\} and Mark Seielstad and Teo, \{Yik Ying\} and Michael Boehnke and Parra, \{Esteban J.\} and Chambers, \{John C.\} and Tai, \{E. Shyong\} and McCarthy, \{Mark I.\} and Morris, \{Andrew P.\}",

note = "Funding Information: Funding for the research undertaken in this study has been received from the following: the Canadian Institutes of Health Research; the European Commission (ENGAGE FP7 HEALTH-F4-2007-201413); the Medical Research Council UK (G0601261); the Mexico Convocatoria (SSA/IMMS/ISSSTE-CONACYT 2012-2, clave 150352, IMSS R-2011-785-018 and CONACYT Salud-2007-C01-71068); the US National Institutes of Health (DK062370, HG000376, DK085584, DK085545, DK073541 and DK085501); and the Wellcome Trust (WT098017, WT090532, WT090367, WT098381, WT081682 and WT085475). We acknowledge the many colleagues who contributed to collection and phenotypic characterization of the clinical samples and the genotyping and analysis of the GWAS data, full details of which are provided in the contributing consortia papers5,11,13,15. We also thank those individuals who agreed to participate in this study.",

year = "2014",

month = mar,

doi = "10.1038/ng.2897",

language = "English (US)",

volume = "46",

pages = "234--244",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

TY - JOUR

T1 - Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

AU - Mahajan, Anubha

AU - Go, Min Jin

AU - Zhang, Weihua

AU - Below, Jennifer E.

AU - Gaulton, Kyle J.

AU - Ferreira, Teresa

AU - Horikoshi, Momoko

AU - Johnson, Andrew D.

AU - Ng, Maggie C Y

AU - Prokopenko, Inga

AU - Saleheen, Danish

AU - Wang, Xu

AU - Zeggini, Eleftheria

AU - Abecasis, Goncalo R.

AU - Adair, Linda S.

AU - Almgren, Peter

AU - Atalay, Mustafa

AU - Aung, Tin

AU - Baldassarre, Damiano

AU - Balkau, Beverley

AU - Bao, Yuqian

AU - Barnett, Anthony H.

AU - Barroso, Ines

AU - Basit, Abdul

AU - Been, Latonya F.

AU - Beilby, John

AU - Bell, Graeme I.

AU - Benediktsson, Rafn

AU - Bergman, Richard N.

AU - OBoehm, Bernhard

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L.

AU - Burtt, Noël

AU - Cai, Qiuyin

AU - Campbell, Harry

AU - Carey, Jason

AU - Cauchi, Stephane

AU - Caulfield, Mark

AU - Chan, Juliana C N

AU - Chang, Li Ching

AU - Chang, Tien Jyun

AU - Chang, Yi Cheng

AU - Charpentier, Guillaume

AU - Chen, Chien Hsiun

AU - Chen, Han

AU - Chen, Yuan Tsong

AU - Chia, Kee Seng

AU - Chidambaram, Manickam

AU - Chines, Peter S.

AU - Cho, Nam H.

AU - Cho, Young Min

AU - Chuang, Lee Ming

AU - Collins, Francis S.

AU - Cornelis, Marilyn C.

AU - Couper, David J.

AU - Crenshaw, Andrew T.

AU - Van Dam, Rob M.

AU - Danesh, John

AU - Das, Debashish

AU - De Faire, Ulf

AU - Dedoussis, George

AU - Deloukas, Panos

AU - Dimas, Antigone S.

AU - Dina, Christian

AU - Doney, Alex S F

AU - Donnelly, Peter J.

AU - Dorkhan, Mozhgan

AU - Van Duijn, Cornelia

AU - Dupuis, Josée

AU - Edkins, Sarah

AU - Elliott, Paul

AU - Emilsson, Valur

AU - Erbel, Raimund

AU - Eriksson, Johan G.

AU - Escobedo, Jorge

AU - Esko, Tonu

AU - Eury, Elodie

AU - Florez, Jose C.

AU - Fontanillas, Pierre

AU - Forouhi, Nita G.

AU - Forsen, Tom

AU - Fox, Caroline

AU - Fraser, Ross M.

AU - Frayling, Timothy M.

AU - Froguel, Philippe

AU - Frossard, Philippe

AU - Gao, Yutang

AU - Gertow, Karl

AU - Gieger, Christian

AU - Gigante, Bruna

AU - Grallert, Harald

AU - Grant, George B.

AU - Groop, Leif C.

AU - Groves, Christopher J.

AU - Grundberg, Elin

AU - Guiducci, Candace

AU - Hamsten, Anders

AU - Han, Bok Ghee

AU - Hara, Kazuo

AU - Hassanali, Neelam

AU - Hattersley, Andrew T.

AU - Hayward, Caroline

AU - Hedman, Asa K.

AU - Herder, Christian

AU - Hofman, Albert

AU - Holmen, Oddgeir L.

AU - Hovingh, Kees

AU - Hreidarsson, Astradur B.

AU - Hu, Cheng

AU - Hu, Frank B.

AU - Hui, Jennie

AU - Humphries, Steve E.

AU - Hunt, Sarah E.

AU - Hunter, David J.

AU - Hveem, Kristian

AU - Hydrie, Zafar I.

AU - Ikegami, Hiroshi

AU - Illig, Thomas

AU - Ingelsson, Erik

AU - Islam, Muhammed

AU - Isomaa, Bo

AU - Jackson, Anne U.

AU - Jafar, Tazeen

AU - James, Alan

AU - Jia, Weiping

AU - Jöckel, Karl Heinz

AU - Jonsson, Anna

AU - Jowett, Jeremy B M

AU - Kadowaki, Takashi

AU - Kang, Hyun Min

AU - Kanoni, Stavroula

AU - Kao, Wen Hong L

AU - Kathiresan, Sekar

AU - Kato, Norihiro

AU - Katulanda, Prasad

AU - Keinanen-Kiukaanniemi, Sirkka M.

AU - Kelly, Ann M.

AU - Khan, Hassan

AU - Khaw, Kay Tee

AU - Khor, Chiea Chuen

AU - Kim, Hyung Lae

AU - Kim, Sangsoo

AU - Kim, Young Jin

AU - Kinnunen, Leena

AU - Klopp, Norman

AU - Kong, Augustine

AU - Korpi-Hyövälti, Eeva

AU - Kowlessur, Sudhir

AU - Kraft, Peter

AU - Kravic, Jasmina

AU - Kristensen, Malene M.

AU - Krithika, S.

AU - Kumar, Ashish

AU - Kumate, Jesus

AU - Kuusisto, Johanna

AU - Kwak, Soo Heon

AU - Laakso, Markku

AU - Lagou, Vasiliki

AU - Lakka, Timo A.

AU - Langenberg, Claudia

AU - Langford, Cordelia

AU - Lawrence, Robert

AU - Leander, Karin

AU - Lee, Jen Mai

AU - Lee, Nanette R.

AU - Li, Man

AU - Li, Xinzhong

AU - Li, Yun

AU - Liang, Junbin

AU - Liju, Samuel

AU - Lim, Wei Yen

AU - Lind, Lars

AU - Lindgren, Cecilia M.

AU - Lindholm, Eero

AU - Liu, Ching Ti

AU - Liu, Jian Jun

AU - Lobbens, Stéphane

AU - Long, Jirong

AU - Loos, Ruth J F

AU - Lu, Wei

AU - Luan, Jianan

AU - Lyssenko, Valeriya

AU - WMa, Ronald C.

AU - Maeda, Shiro

AU - Mägi, Reedik

AU - Männistö, Satu

AU - Matthews, David R.

AU - Meigs, James B.

AU - Melander, Olle

AU - Metspalu, Andres

AU - Meyer, Julia

AU - Mirza, Ghazala

AU - Mihailov, Evelin

AU - Moebus, Susanne

AU - Mohan, Viswanathan

AU - Mohlke, Karen L.

AU - Morris, Andrew D.

AU - WMühleisen, Thomas

AU - Müller-Nurasyid, Martina

AU - Musk, Bill

AU - Nakamura, Jiro

AU - Nakashima, Eitaro

AU - Navarro, Pau

AU - Ng, Peng Keat

AU - Nica, Alexandra C.

AU - Nilsson, Peter M.

AU - Njølstad, Inger

AU - Nöthen, Markus M.

AU - Ohnaka, Keizo

AU - Ong, Twee Hee

AU - Owen, Katharine R.

AU - Palmer, Colin N A

AU - Pankow, James S.

AU - Park, Kyong Soo

AU - Parkin, Melissa

AU - Pechlivanis, Sonali

AU - Pedersen, Nancy L.

AU - Peltonen, Leena

AU - Perry, John R B

AU - Peters, Annette

AU - Pinidiyapathirage, Janani M.

AU - Platou, Carl G P

AU - Potter, Simon

AU - Price, Jackie F.

AU - Qi, Lu

AU - Radha, Venkatesan

AU - Rallidis, Loukianos

AU - Rasheed, Asif

AU - Rathmann, Wolfgang

AU - Rauramaa, Rainer

AU - Raychaudhuri, Soumya

AU - Rayner, N. William

AU - Rees, Simon D.

AU - Rehnberg, Emil

AU - Ripatti, Samuli

AU - Robertson, Neil

AU - Roden, Michael

AU - Rossin, Elizabeth J.

AU - Rudan, Igor

AU - Rybin, Denis

AU - Saaristo, Timo E.

AU - Salomaa, Veikko

AU - Saltevo, Juha

AU - Samuel, Maria

AU - KSanghera, Dharambir

AU - Saramies, Jouko

AU - Scott, James

AU - Scott, Laura J.

AU - Scott, Robert A.

AU - Segrè, Ayellet V.

AU - Sehmi, Joban

AU - Sennblad, Bengt

AU - Shah, Nabi

AU - Shah, Sonia

AU - Shera, A. Samad

AU - Shu, Xiao Ou

AU - Shuldiner, Alan R.

AU - Sigurosson, Gunnar

AU - Sijbrands, Eric

AU - Silveira, Angela

AU - Sim, Xueling

AU - Sivapalaratnam, Suthesh

AU - Small, Kerrin S.

AU - So, Wing Yee

AU - Stančáková, Alena

AU - Stefansson, Kari

AU - Steinbach, Gerald

AU - Steinthorsdottir, Valgerdur

AU - Stirrups, Kathleen

AU - Strawbridge, Rona J.

AU - Stringham, Heather M.

AU - Sun, Qi

AU - Suo, Chen

AU - Syvänen, Ann Christine

AU - Takayanagi, Ryoichi

AU - Takeuchi, Fumihiko

AU - Tay, Wan Ting

AU - Teslovich, Tanya M.

AU - Thorand, Barbara

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Tikkanen, Emmi

AU - Trakalo, Joseph

AU - Tremoli, Elena

AU - Trip, Mieke D.

AU - Tsai, Fuu Jen

AU - Tuomi, Tiinamaija

AU - Tuomilehto, Jaakko

AU - Uitterlinden, Andre G.

AU - Valladares-Salgado, Adan

AU - Vedantam, Sailaja

AU - Veglia, Fabrizio

AU - Voight, Benjamin F.

AU - Wang, Congrong

AU - Wareham, Nicholas J.

AU - Wennauer, Roman

AU - Wickremasinghe, Ananda R.

AU - Wilsgaard, Tom

AU - Wilson, James F.

AU - Wiltshire, Steven

AU - Winckler, Wendy

AU - Wong, Tien Yin

AU - Wood, Andrew R.

AU - Wu, Jer Yuarn

AU - Wu, Ying

AU - Yamamoto, Ken

AU - Yamauchi, Toshimasa

AU - Yang, Mingyu

AU - Yengo, Loic

AU - Yokota, Mitsuhiro

AU - Young, Robin

AU - Zabaneh, Delilah

AU - Zhang, Fan

AU - Zhang, Rong

AU - Zheng, Wei

AU - Zimmet, Paul Z.

AU - Altshuler, David

AU - Bowden, Donald W.

AU - Cho, Yoon Shin

AU - Cox, Nancy J.

AU - Cruz, Miguel

AU - Hanis, Craig L.

AU - Kooner, Jaspal

AU - Lee, Jong Young

AU - Seielstad, Mark

AU - Teo, Yik Ying

AU - Boehnke, Michael

AU - Parra, Esteban J.

AU - Chambers, John C.

AU - Tai, E. Shyong

AU - McCarthy, Mark I.

AU - Morris, Andrew P.

N1 - Funding Information: Funding for the research undertaken in this study has been received from the following: the Canadian Institutes of Health Research; the European Commission (ENGAGE FP7 HEALTH-F4-2007-201413); the Medical Research Council UK (G0601261); the Mexico Convocatoria (SSA/IMMS/ISSSTE-CONACYT 2012-2, clave 150352, IMSS R-2011-785-018 and CONACYT Salud-2007-C01-71068); the US National Institutes of Health (DK062370, HG000376, DK085584, DK085545, DK073541 and DK085501); and the Wellcome Trust (WT098017, WT090532, WT090367, WT098381, WT081682 and WT085475). We acknowledge the many colleagues who contributed to collection and phenotypic characterization of the clinical samples and the genotyping and analysis of the GWAS data, full details of which are provided in the contributing consortia papers5,11,13,15. We also thank those individuals who agreed to participate in this study.

PY - 2014/3

Y1 - 2014/3

N2 - To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

AB - To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

UR - https://www.scopus.com/pages/publications/84895868553

UR - https://www.scopus.com/pages/publications/84895868553#tab=citedBy

U2 - 10.1038/ng.2897

DO - 10.1038/ng.2897

M3 - Article

C2 - 24509480

AN - SCOPUS:84895868553

SN - 1061-4036

VL - 46

SP - 234

EP - 244

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

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