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

A Mahajan; MJ Go; WH Zhang; JE Below; KJ Gaulton; T Ferreira; M Horikoshi; AD Johnson; MCY Ng; I Prokopenko; D Saleheen; X Wang; E Zeggini; GR Abecasis; LS Adair; P Almgren; M Atalay; T Aung; D Baldassarre; B Balkau; YQ Bao; AH Barnett; I Barroso; A Basit; Loes Been; J Beilby; GI Bell; R Benediktsson; RN Bergman; BO Boehm; E Boerwinkle; LL Bonnycastle; N Burtt; QY Cai; H Campbell; J Carey; S Cauchi; M Caulfield; JCN Chan; LC Chang; TJ Chang; YC Chang; G Charpentier; Chia-hui Chen; H Chen; YT Chen; KS Chia; M Chidambaram; PS Chines; NH Cho; YM Cho; LM Chuang; FS Collins; MC Cornelis; DJ Couper; AT Crenshaw; RM van Dam; J Danesh; Devashish Das; U de Faire; G Dedoussis; P Deloukas; AS Dimas; C Dina; ASF Doney; PJ Donnelly; M Dorkhan; Cornelia Duijn; J Dupuis; S Edkins; P Elliott; V Emilsson; R Erbel; JG Eriksson; J Escobedo; T Esko; E Eury; JC Florez; P Fontanillas; NG Forouhi; T Forsen; C Fox; RM Fraser; TM Frayling; P Froguel; P Frossard; YT Gao; K Gertow; C Gieger; B Gigante; H Grallert; GB Grant; LC Groop; CJ Groves; E Grundberg; C Guiducci; A Hamsten; BG Han; K Hara; N Hassanali; AT Hattersley; C Hayward; AK Hedman; Cindy Herder; Bert Hofman; OL Holmen; K Hovingh; AB Hreidarsson; C Hu; FB Hu; J Hui; SE Humphries; SE Hunt; DJ Hunter; K Hveem; ZI Hydrie; H Ikegami; T Illig; E Ingelsson; M Islam; B Isomaa; AU Jackson; T Jafar; A James; WP Jia; KH Jockel; A Jonsson; JBM Jowett; T Kadowaki; HM Kang; S Kanoni; WHL Kao; S Kathiresan; N Kato; P Katulanda; SM Keinanen-Kiukaanniemi; AM Kelly; H Khan; KT Khaw; CC Khor; HL Kim; S Kim; YJ Kim; L Kinnunen; N Klopp; A Kong; E Korpi-Hyovalti; S Kowlessur; P Kraft; J Kravic; MM Kristensen; S Krithika; A Kumar; J Kumate; J Kuusisto; SH Kwak; M Laakso; V Lagou; TA Lakka; C Langenberg; C Langford; R Lawrence; K Leander; JM Lee; NR Lee; M Li; XZ Li; Y Li; JB Liang; S Liju; WY Lim; L Lind; CM Lindgren; E Lindholm; CT Liu; JJ Liu; S Lobbens; JR Long; RJF Loos; W Lu; JA Luan; V Lyssenko; RCW Ma; S Maeda; R Magi; S Mannisto; DR Matthews; JB Meigs; O Melander; A Metspalu; J Meyer; G Mirza; E Mihailov; S Moebus; V Mohan; KL Mohlke; AD Morris; TW Muhleisen; M Muller-Nurasyid; B Musk; J Nakamura; E Nakashima; P Navarro; PK Ng; AC Nica; PM Nilsson; I Njolstad; MM Nothen; K Ohnaka; TH Ong; KR Owen; CNA Palmer; JS Pankow; KS Park; M Parkin; S Pechlivanis; NL Pedersen; L Peltonen; JRB Perry; A Peters; JM Pinidiyapathirage; CGP Platou; S Potter; JF Price; L Qi; V Radha; L Rallidis; A Rasheed; W Rathmann; R Rauramaa; S Raychaudhuri; NW Rayner; SD Rees; E Rehnberg; S Ripatti; N Robertson; M Roden; EJ Rossin; I Rudan; D Rybin; TE Saaristo; V Salomaa; J Saltevo; M Samuel; DK Sanghera; J Saramies; J Scott; LJ Scott; RA Scott; AV Segre; J Sehmi; B Sennblad; N Shah; S Shah; AS Shera; XO Shu; AR Shuldiner; G Sigurdsson; E.J.G. Sijbrands; A Silveira; X Sim; S Sivapalaratnam; KS Small; WY So; A Stancakova; K Stefansson; G Steinbach; V Steinthorsdottir; K Stirrups; RJ Strawbridge; HM Stringham; Q Sun; C Suo; AC Syvanen; R Takayanagi; F Takeuchi; WT Tay; TM Teslovich; B Thorand; G Thorleifsson; U Thorsteinsdottir; E Tikkanen; J Trakalo; E Tremoli; MD Trip; FJ Tsai; T Tuomi; J Tuomilehto; André Uitterlinden; A Valladares-Salgado; S Vedantam; F Veglia; BF Voight; CR Wang; NJ Wareham; R Wennauer; AR Wickremasinghe; T Wilsgaard; JF Wilson; S Wiltshire; W Winckler; TY (Tien Yin) Wong; AR Wood; JY Wu; Fenny Wu; K Yamamoto; T Yamauchi; MY Yang; L Yengo; M Yokota; R Young; D Zabaneh; F Zhang; R Zhang; W Zheng; PZ Zimmet; D Altshuler; DW Bowden; YS Cho; NJ Cox; M Cruz; CL Hanis; J Kooner; JY Lee; M Seielstad; YY Teo; M Boehnke; EJ Parra; JC Chambers; ES Tai; MI McCarthy; AP Morris

doi:10.1038/ng.2897

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

A Mahajan, MJ Go, WH Zhang, JE Below, KJ Gaulton, T Ferreira, M Horikoshi, AD Johnson, MCY Ng, I Prokopenko, D Saleheen, X Wang, E Zeggini, GR Abecasis, LS Adair, P Almgren, M Atalay, T Aung, D Baldassarre, B BalkauYQ Bao, AH Barnett, I Barroso, A Basit, Loes Been, J Beilby, GI Bell, R Benediktsson, RN Bergman, BO Boehm, E Boerwinkle, LL Bonnycastle, N Burtt, QY Cai, H Campbell, J Carey, S Cauchi, M Caulfield, JCN Chan, LC Chang, TJ Chang, YC Chang, G Charpentier, Chia-hui Chen, H Chen, YT Chen, KS Chia, M Chidambaram, PS Chines, NH Cho, YM Cho, LM Chuang, FS Collins, MC Cornelis, DJ Couper, AT Crenshaw, RM van Dam, J Danesh, Devashish Das, U de Faire, G Dedoussis, P Deloukas, AS Dimas, C Dina, ASF Doney, PJ Donnelly, M Dorkhan, Cornelia Duijn, J Dupuis, S Edkins, P Elliott, V Emilsson, R Erbel, JG Eriksson, J Escobedo, T Esko, E Eury, JC Florez, P Fontanillas, NG Forouhi, T Forsen, C Fox, RM Fraser, TM Frayling, P Froguel, P Frossard, YT Gao, K Gertow, C Gieger, B Gigante, H Grallert, GB Grant, LC Groop, CJ Groves, E Grundberg, C Guiducci, A Hamsten, BG Han, K Hara, N Hassanali, AT Hattersley, C Hayward, AK Hedman, Cindy Herder, Bert Hofman, OL Holmen, K Hovingh, AB Hreidarsson, C Hu, FB Hu, J Hui, SE Humphries, SE Hunt, DJ Hunter, K Hveem, ZI Hydrie, H Ikegami, T Illig, E Ingelsson, M Islam, B Isomaa, AU Jackson, T Jafar, A James, WP Jia, KH Jockel, A Jonsson, JBM Jowett, T Kadowaki, HM Kang, S Kanoni, WHL Kao, S Kathiresan, N Kato, P Katulanda, SM Keinanen-Kiukaanniemi, AM Kelly, H Khan, KT Khaw, CC Khor, HL Kim, S Kim, YJ Kim, L Kinnunen, N Klopp, A Kong, E Korpi-Hyovalti, S Kowlessur, P Kraft, J Kravic, MM Kristensen, S Krithika, A Kumar, J Kumate, J Kuusisto, SH Kwak, M Laakso, V Lagou, TA Lakka, C Langenberg, C Langford, R Lawrence, K Leander, JM Lee, NR Lee, M Li, XZ Li, Y Li, JB Liang, S Liju, WY Lim, L Lind, CM Lindgren, E Lindholm, CT Liu, JJ Liu, S Lobbens, JR Long, RJF Loos, W Lu, JA Luan, V Lyssenko, RCW Ma, S Maeda, R Magi, S Mannisto, DR Matthews, JB Meigs, O Melander, A Metspalu, J Meyer, G Mirza, E Mihailov, S Moebus, V Mohan, KL Mohlke, AD Morris, TW Muhleisen, M Muller-Nurasyid, B Musk, J Nakamura, E Nakashima, P Navarro, PK Ng, AC Nica, PM Nilsson, I Njolstad, MM Nothen, K Ohnaka, TH Ong, KR Owen, CNA Palmer, JS Pankow, KS Park, M Parkin, S Pechlivanis, NL Pedersen, L Peltonen, JRB Perry, A Peters, JM Pinidiyapathirage, CGP Platou, S Potter, JF Price, L Qi, V Radha, L Rallidis, A Rasheed, W Rathmann, R Rauramaa, S Raychaudhuri, NW Rayner, SD Rees, E Rehnberg, S Ripatti, N Robertson, M Roden, EJ Rossin, I Rudan, D Rybin, TE Saaristo, V Salomaa, J Saltevo, M Samuel, DK Sanghera, J Saramies, J Scott, LJ Scott, RA Scott, AV Segre, J Sehmi, B Sennblad, N Shah, S Shah, AS Shera, XO Shu, AR Shuldiner, G Sigurdsson, E.J.G. Sijbrands, A Silveira, X Sim, S Sivapalaratnam, KS Small, WY So, A Stancakova, K Stefansson, G Steinbach, V Steinthorsdottir, K Stirrups, RJ Strawbridge, HM Stringham, Q Sun, C Suo, AC Syvanen, R Takayanagi, F Takeuchi, WT Tay, TM Teslovich, B Thorand, G Thorleifsson, U Thorsteinsdottir, E Tikkanen, J Trakalo, E Tremoli, MD Trip, FJ Tsai, T Tuomi, J Tuomilehto, André Uitterlinden, A Valladares-Salgado, S Vedantam, F Veglia, BF Voight, CR Wang, NJ Wareham, R Wennauer, AR Wickremasinghe, T Wilsgaard, JF Wilson, S Wiltshire, W Winckler, TY (Tien Yin) Wong, AR Wood, JY Wu, Fenny Wu, K Yamamoto, T Yamauchi, MY Yang, L Yengo, M Yokota, R Young, D Zabaneh, F Zhang, R Zhang, W Zheng, PZ Zimmet, D Altshuler, DW Bowden, YS Cho, NJ Cox, M Cruz, CL Hanis, J Kooner, JY Lee, M Seielstad, YY Teo, M Boehnke, EJ Parra, JC Chambers, ES Tai, MI McCarthy, AP Morris

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

837 Citations (Scopus)

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	Undefined/Unknown
Pages (from-to)	234-+
Journal	Nature Genetics
Volume	46
Issue number	3
DOIs	https://doi.org/10.1038/ng.2897
Publication status	Published - 2014

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EMC COEUR-09
EMC MM-01-39-09-A
EMC NIHES-01-64-02

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Access to Document

10.1038/ng.2897

Cite this

Mahajan, A., Go, MJ., Zhang, WH., 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., ... Morris, AP. (2014). Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nature Genetics, 46(3), 234-+. https://doi.org/10.1038/ng.2897

@article{a2aa95999f744396840c07ec12934a7a,

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 = "A Mahajan and MJ Go and WH Zhang and JE Below and KJ Gaulton and T Ferreira and M Horikoshi and AD Johnson and MCY Ng and I Prokopenko and D Saleheen and X Wang and E Zeggini and GR Abecasis and LS Adair and P Almgren and M Atalay and T Aung and D Baldassarre and B Balkau and YQ Bao and AH Barnett and I Barroso and A Basit and Loes Been and J Beilby and GI Bell and R Benediktsson and RN Bergman and BO Boehm and E Boerwinkle and LL Bonnycastle and N Burtt and QY Cai and H Campbell and J Carey and S Cauchi and M Caulfield and JCN Chan and LC Chang and TJ Chang and YC Chang and G Charpentier and Chia-hui Chen and H Chen and YT Chen and KS Chia and M Chidambaram and PS Chines and NH Cho and YM Cho and LM Chuang and FS Collins and MC Cornelis and DJ Couper and AT Crenshaw and {van Dam}, RM and J Danesh and Devashish Das and {de Faire}, U and G Dedoussis and P Deloukas and AS Dimas and C Dina and ASF Doney and PJ Donnelly and M Dorkhan and Cornelia Duijn and J Dupuis and S Edkins and P Elliott and V Emilsson and R Erbel and JG Eriksson and J Escobedo and T Esko and E Eury and JC Florez and P Fontanillas and NG Forouhi and T Forsen and C Fox and RM Fraser and TM Frayling and P Froguel and P Frossard and YT Gao and K Gertow and C Gieger and B Gigante and H Grallert and GB Grant and LC Groop and CJ Groves and E Grundberg and C Guiducci and A Hamsten and BG Han and K Hara and N Hassanali and AT Hattersley and C Hayward and AK Hedman and Cindy Herder and Bert Hofman and OL Holmen and K Hovingh and AB Hreidarsson and C Hu and FB Hu and J Hui and SE Humphries and SE Hunt and DJ Hunter and K Hveem and ZI Hydrie and H Ikegami and T Illig and E Ingelsson and M Islam and B Isomaa and AU Jackson and T Jafar and A James and WP Jia and KH Jockel and A Jonsson and JBM Jowett and T Kadowaki and HM Kang and S Kanoni and WHL Kao and S Kathiresan and N Kato and P Katulanda and SM Keinanen-Kiukaanniemi and AM Kelly and H Khan and KT Khaw and CC Khor and HL Kim and S Kim and YJ Kim and L Kinnunen and N Klopp and A Kong and E Korpi-Hyovalti and S Kowlessur and P Kraft and J Kravic and MM Kristensen and S Krithika and A Kumar and J Kumate and J Kuusisto and SH Kwak and M Laakso and V Lagou and TA Lakka and C Langenberg and C Langford and R Lawrence and K Leander and JM Lee and NR Lee and M Li and XZ Li and Y Li and JB Liang and S Liju and WY Lim and L Lind and CM Lindgren and E Lindholm and CT Liu and JJ Liu and S Lobbens and JR Long and RJF Loos and W Lu and JA Luan and V Lyssenko and RCW Ma and S Maeda and R Magi and S Mannisto and DR Matthews and JB Meigs and O Melander and A Metspalu and J Meyer and G Mirza and E Mihailov and S Moebus and V Mohan and KL Mohlke and AD Morris and TW Muhleisen and M Muller-Nurasyid and B Musk and J Nakamura and E Nakashima and P Navarro and PK Ng and AC Nica and PM Nilsson and I Njolstad and MM Nothen and K Ohnaka and TH Ong and KR Owen and CNA Palmer and JS Pankow and KS Park and M Parkin and S Pechlivanis and NL Pedersen and L Peltonen and JRB Perry and A Peters and JM Pinidiyapathirage and CGP Platou and S Potter and JF Price and L Qi and V Radha and L Rallidis and A Rasheed and W Rathmann and R Rauramaa and S Raychaudhuri and NW Rayner and SD Rees and E Rehnberg and S Ripatti and N Robertson and M Roden and EJ Rossin and I Rudan and D Rybin and TE Saaristo and V Salomaa and J Saltevo and M Samuel and DK Sanghera and J Saramies and J Scott and LJ Scott and RA Scott and AV Segre and J Sehmi and B Sennblad and N Shah and S Shah and AS Shera and XO Shu and AR Shuldiner and G Sigurdsson and E.J.G. Sijbrands and A Silveira and X Sim and S Sivapalaratnam and KS Small and WY So and A Stancakova and K Stefansson and G Steinbach and V Steinthorsdottir and K Stirrups and RJ Strawbridge and HM Stringham and Q Sun and C Suo and AC Syvanen and R Takayanagi and F Takeuchi and WT Tay and TM Teslovich and B Thorand and G Thorleifsson and U Thorsteinsdottir and E Tikkanen and J Trakalo and E Tremoli and MD Trip and FJ Tsai and T Tuomi and J Tuomilehto and Andr{\'e} Uitterlinden and A Valladares-Salgado and S Vedantam and F Veglia and BF Voight and CR Wang and NJ Wareham and R Wennauer and AR Wickremasinghe and T Wilsgaard and JF Wilson and S Wiltshire and W Winckler and Wong, {TY (Tien Yin)} and AR Wood and JY Wu and Fenny Wu and K Yamamoto and T Yamauchi and MY Yang and L Yengo and M Yokota and R Young and D Zabaneh and F Zhang and R Zhang and W Zheng and PZ Zimmet and D Altshuler and DW Bowden and YS Cho and NJ Cox and M Cruz and CL Hanis and J Kooner and JY Lee and M Seielstad and YY Teo and M Boehnke and EJ Parra and JC Chambers and ES Tai and MI McCarthy and AP Morris",

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doi = "10.1038/ng.2897",

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Mahajan, A, Go, MJ, Zhang, WH, 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, YQ, Barnett, AH, Barroso, I, Basit, A, Been, L, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, Boehm, BO, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, QY, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, LC, Chang, TJ, Chang, YC, Charpentier, G, Chen, C, 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, 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, YT, 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, B, 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, WP, Jockel, 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-Hyovalti, 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, XZ, Li, Y, Liang, JB, Liju, S, Lim, WY, Lind, L, Lindgren, CM, Lindholm, E, Liu, CT, Liu, JJ, Lobbens, S, Long, JR, Loos, RJF, Lu, W, Luan, JA, Lyssenko, V, Ma, RCW, Maeda, S, Magi, R, Mannisto, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, Muhleisen, TW, Muller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Ng, PK, Nica, AC, Nilsson, PM, Njolstad, I, Nothen, 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, Sanghera, DK, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segre, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurdsson, G, Sijbrands, EJG, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stancakova, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvanen, 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, A, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, CR, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, JY, Wu, F, Yamamoto, K, Yamauchi, T, Yang, MY, 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-+. https://doi.org/10.1038/ng.2897

TY - JOUR

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

AU - Mahajan, A

AU - Go, MJ

AU - Zhang, WH

AU - Below, JE

AU - Gaulton, KJ

AU - Ferreira, T

AU - Horikoshi, M

AU - Johnson, AD

AU - Ng, MCY

AU - Prokopenko, I

AU - Saleheen, D

AU - Wang, X

AU - Zeggini, E

AU - Abecasis, GR

AU - Adair, LS

AU - Almgren, P

AU - Atalay, M

AU - Aung, T

AU - Baldassarre, D

AU - Balkau, B

AU - Bao, YQ

AU - Barnett, AH

AU - Barroso, I

AU - Basit, A

AU - Been, Loes

AU - Beilby, J

AU - Bell, GI

AU - Benediktsson, R

AU - Bergman, RN

AU - Boehm, BO

AU - Boerwinkle, E

AU - Bonnycastle, LL

AU - Burtt, N

AU - Cai, QY

AU - Campbell, H

AU - Carey, J

AU - Cauchi, S

AU - Caulfield, M

AU - Chan, JCN

AU - Chang, LC

AU - Chang, TJ

AU - Chang, YC

AU - Charpentier, G

AU - Chen, Chia-hui

AU - Chen, H

AU - Chen, YT

AU - Chia, KS

AU - Chidambaram, M

AU - Chines, PS

AU - Cho, NH

AU - Cho, YM

AU - Chuang, LM

AU - Collins, FS

AU - Cornelis, MC

AU - Couper, DJ

AU - Crenshaw, AT

AU - van Dam, RM

AU - Danesh, J

AU - Das, Devashish

AU - de Faire, U

AU - Dedoussis, G

AU - Deloukas, P

AU - Dimas, AS

AU - Dina, C

AU - Doney, ASF

AU - Donnelly, PJ

AU - Dorkhan, M

AU - Duijn, Cornelia

AU - Dupuis, J

AU - Edkins, S

AU - Elliott, P

AU - Emilsson, V

AU - Erbel, R

AU - Eriksson, JG

AU - Escobedo, J

AU - Esko, T

AU - Eury, E

AU - Florez, JC

AU - Fontanillas, P

AU - Forouhi, NG

AU - Forsen, T

AU - Fox, C

AU - Fraser, RM

AU - Frayling, TM

AU - Froguel, P

AU - Frossard, P

AU - Gao, YT

AU - Gertow, K

AU - Gieger, C

AU - Gigante, B

AU - Grallert, H

AU - Grant, GB

AU - Groop, LC

AU - Groves, CJ

AU - Grundberg, E

AU - Guiducci, C

AU - Hamsten, A

AU - Han, BG

AU - Hara, K

AU - Hassanali, N

AU - Hattersley, AT

AU - Hayward, C

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PY - 2014

Y1 - 2014

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.

U2 - 10.1038/ng.2897

DO - 10.1038/ng.2897

M3 - Article

C2 - 24509480

SN - 1061-4036

VL - 46

SP - 234-+

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -