Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

A.P. Morris; B.F. Voight; T.M. Teslovich; T. Ferreira; A.V. Segrè; V. Steinthorsdottir; R.J. Strawbridge; H. Khan; H. Grallert; A. Mahajan; I. Prokopenko; H.M. Kang; C. Dina; T. Esko; R.M. Fraser; S. Kanoni; A. Kumar; V. Lagou; C. Langenberg; J. Luan; C.M. Lindgren; M. Müller-Nurasyid; S. Pechlivanis; N.W. Rayner; L.J. Scott; S. Wiltshire; L. Yengo; L. Kinnunen; E.J. Rossin; S. Raychaudhuri; A.D. Johnson; A.S. Dimas; R.J.F. Loos; S. Vedantam; H. Chen; J.C. Florez; C. Fox; C.-T. Liu; D. Rybin; D.J. Couper; W.H.L. Kao; M. Li; M.C. Cornelis; P. Kraft; Q. Sun; R.M. Van Dam; H.M. Stringham; P.S. Chines; K. Fischer; P. Fontanillas; O.L. Holmen; S.E. Hunt; A.U. Jackson; A. Kong; Robert Lawrence; J. Meyer; J.R.B. Perry; C.G.P. Platou; S. Potter; E. Rehnberg; N. Robertson; S. Sivapalaratnam; A. Stančáková; K. Stirrups; G. Thorleifsson; E. Tikkanen; A.R. Wood; P. Almgren; M. Atalay; R. Benediktsson; L.L. Bonnycastle; N. Burtt; J. Carey; G. Charpentier; A.T. Crenshaw; A.S.F. Doney; M. Dorkhan; S. Edkins; V. Emilsson; E. Eury; T. Forsen; K. Gertow; B. Gigante; G.B. Grant; C.J. Groves; C. Guiducci; C. Herder; A.B. Hreidarsson; Jennie Hui; Alan James; A. Jonsson; W. Rathmann; N. Klopp; J. Kravic; K. Krjutškov; C. Langford; K. Leander; E. Lindholm; S. Lobbens; S. Männistö; G. Mirza; T.W. Mühleisen; B. Musk; M. Parkin; L. Rallidis; J. Saramies; B. Sennblad; S. Shah; G. Sigursson; A. Silveira; G. Steinbach; B. Thorand; J. Trakalo; F. Veglia; R. Wennauer; W. Winckler; D. Zabaneh; H. Campbell; C. Van Duijn; A.G. Uitterlinden; A. Hofman; E. Sijbrands; G.R. Abecasis; K.R. Owen; E. Zeggini; M.D. Trip; N.G. Forouhi; A.-C. Syvänen; J.G. Eriksson; L. Peltonen; M.M. Nöthen; B. Balkau; C.N.A. Palmer; V. Lyssenko; T. Tuomi; B. Isomaa; D.J. Hunter; L. Qi; A.R. Shuldiner; M. Roden; I. Barroso; T. Wilsgaard; John Beilby; K. Hovingh; J.F. Price; J.F. Wilson; R. Rauramaa; T.A. Lakka; L. Lind; G. Dedoussis; I. Njølstad; N.L. Pedersen; K.-T. Khaw; N.J. Wareham; S.M. Keinanen-Kiukaanniemi; T.E. Saaristo; E. Korpi-Hyövälti; J. Saltevo; M. Laakso; J. Kuusisto; A. Metspalu; F.S. Collins; K.L. Mohlke; R.N. Bergman; J. Tuomilehto; B.O. Boehm; C. Gieger; K. Hveem; S. Cauchi; P. Froguel; D. Baldassarre; E. Tremoli; S.E. Humphries; D. Saleheen; J. Danesh; E. Ingelsson; S. Ripatti; V. Salomaa; R. Erbel; K.-H. Jöckel; S. Moebus; A. Peters; T. Illig; U.D. Faire; A. Hamsten; A.D. Morris; P.J. Donnelly; T.M. Frayling; A.T. Hattersley; E. Boerwinkle; O. Melander; S. Kathiresan; P.M. Nilsson; P. Deloukas; U. Thorsteinsdottir; L.C. Groop; K. Stefansson; F. Hu; J.S. Pankow; J. Dupuis; J.B. Meigs; D. Altshuler; M. Boehnke; M.I. Mccarthy

doi:10.1038/ng.2383

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

A.P. Morris, B.F. Voight, T.M. Teslovich, T. Ferreira, A.V. Segrè, V. Steinthorsdottir, R.J. Strawbridge, H. Khan, H. Grallert, A. Mahajan, I. Prokopenko, H.M. Kang, C. Dina, T. Esko, R.M. Fraser, S. Kanoni, A. Kumar, V. Lagou, C. Langenberg, J. LuanC.M. Lindgren, M. Müller-Nurasyid, S. Pechlivanis, N.W. Rayner, L.J. Scott, S. Wiltshire, L. Yengo, L. Kinnunen, E.J. Rossin, S. Raychaudhuri, A.D. Johnson, A.S. Dimas, R.J.F. Loos, S. Vedantam, H. Chen, J.C. Florez, C. Fox, C.-T. Liu, D. Rybin, D.J. Couper, W.H.L. Kao, M. Li, M.C. Cornelis, P. Kraft, Q. Sun, R.M. Van Dam, H.M. Stringham, P.S. Chines, K. Fischer, P. Fontanillas, O.L. Holmen, S.E. Hunt, A.U. Jackson, A. Kong, Robert Lawrence, J. Meyer, J.R.B. Perry, C.G.P. Platou, S. Potter, E. Rehnberg, N. Robertson, S. Sivapalaratnam, A. Stančáková, K. Stirrups, G. Thorleifsson, E. Tikkanen, A.R. Wood, P. Almgren, M. Atalay, R. Benediktsson, L.L. Bonnycastle, N. Burtt, J. Carey, G. Charpentier, A.T. Crenshaw, A.S.F. Doney, M. Dorkhan, S. Edkins, V. Emilsson, E. Eury, T. Forsen, K. Gertow, B. Gigante, G.B. Grant, C.J. Groves, C. Guiducci, C. Herder, A.B. Hreidarsson, Jennie Hui, Alan James, A. Jonsson, W. Rathmann, N. Klopp, J. Kravic, K. Krjutškov, C. Langford, K. Leander, E. Lindholm, S. Lobbens, S. Männistö, G. Mirza, T.W. Mühleisen, B. Musk, M. Parkin, L. Rallidis, J. Saramies, B. Sennblad, S. Shah, G. Sigursson, A. Silveira, G. Steinbach, B. Thorand, J. Trakalo, F. Veglia, R. Wennauer, W. Winckler, D. Zabaneh, H. Campbell, C. Van Duijn, A.G. Uitterlinden, A. Hofman, E. Sijbrands, G.R. Abecasis, K.R. Owen, E. Zeggini, M.D. Trip, N.G. Forouhi, A.-C. Syvänen, J.G. Eriksson, L. Peltonen, M.M. Nöthen, B. Balkau, C.N.A. Palmer, V. Lyssenko, T. Tuomi, B. Isomaa, D.J. Hunter, L. Qi, A.R. Shuldiner, M. Roden, I. Barroso, T. Wilsgaard, John Beilby, K. Hovingh, J.F. Price, J.F. Wilson, R. Rauramaa, T.A. Lakka, L. Lind, G. Dedoussis, I. Njølstad, N.L. Pedersen, K.-T. Khaw, N.J. Wareham, S.M. Keinanen-Kiukaanniemi, T.E. Saaristo, E. Korpi-Hyövälti, J. Saltevo, M. Laakso, J. Kuusisto, A. Metspalu, F.S. Collins, K.L. Mohlke, R.N. Bergman, J. Tuomilehto, B.O. Boehm, C. Gieger, K. Hveem, S. Cauchi, P. Froguel, D. Baldassarre, E. Tremoli, S.E. Humphries, D. Saleheen, J. Danesh, E. Ingelsson, S. Ripatti, V. Salomaa, R. Erbel, K.-H. Jöckel, S. Moebus, A. Peters, T. Illig, U.D. Faire, A. Hamsten, A.D. Morris, P.J. Donnelly, T.M. Frayling, A.T. Hattersley, E. Boerwinkle, O. Melander, S. Kathiresan, P.M. Nilsson, P. Deloukas, U. Thorsteinsdottir, L.C. Groop, K. Stefansson, F. Hu, J.S. Pankow, J. Dupuis, J.B. Meigs, D. Altshuler, M. Boehnke, M.I. Mccarthy

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

1544 Citations (Scopus)

Abstract

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

Original language	English
Pages (from-to)	981-92
Journal	Nature Genetics
Volume	44
Issue number	9
Early online date	12 Aug 2012
DOIs	https://doi.org/10.1038/ng.2383
Publication status	Published - 1 Sept 2012

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10.1038/ng.2383

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442244/

Cite this

Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., Mahajan, A., Prokopenko, I., Kang, H. M., Dina, C., Esko, T., Fraser, R. M., Kanoni, S., Kumar, A., Lagou, V., Langenberg, C., ... Mccarthy, M. I. (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-92. https://doi.org/10.1038/ng.2383

@article{a60b699109874957afaae23efa2be905,

title = "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes",

abstract = "To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.",

author = "A.P. Morris and B.F. Voight and T.M. Teslovich and T. Ferreira and A.V. Segr{\`e} and V. Steinthorsdottir and R.J. Strawbridge and H. Khan and H. Grallert and A. Mahajan and I. Prokopenko and H.M. Kang and C. Dina and T. Esko and R.M. Fraser and S. Kanoni and A. Kumar and V. Lagou and C. Langenberg and J. Luan and C.M. Lindgren and M. M{\"u}ller-Nurasyid and S. Pechlivanis and N.W. Rayner and L.J. Scott and S. Wiltshire and L. Yengo and L. Kinnunen and E.J. Rossin and S. Raychaudhuri and A.D. Johnson and A.S. Dimas and R.J.F. Loos and S. Vedantam and H. Chen and J.C. Florez and C. Fox and C.-T. Liu and D. Rybin and D.J. Couper and W.H.L. Kao and M. Li and M.C. Cornelis and P. Kraft and Q. Sun and {Van Dam}, R.M. and H.M. Stringham and P.S. Chines and K. Fischer and P. Fontanillas and O.L. Holmen and S.E. Hunt and A.U. Jackson and A. Kong and Robert Lawrence and J. Meyer and J.R.B. Perry and C.G.P. Platou and S. Potter and E. Rehnberg and N. Robertson and S. Sivapalaratnam and A. Stan{\v c}{\'a}kov{\'a} and K. Stirrups and G. Thorleifsson and E. Tikkanen and A.R. Wood and P. Almgren and M. Atalay and R. Benediktsson and L.L. Bonnycastle and N. Burtt and J. Carey and G. Charpentier and A.T. Crenshaw and A.S.F. Doney and M. Dorkhan and S. Edkins and V. Emilsson and E. Eury and T. Forsen and K. Gertow and B. Gigante and G.B. Grant and C.J. Groves and C. Guiducci and C. Herder and A.B. Hreidarsson and Jennie Hui and Alan James and A. Jonsson and W. Rathmann and N. Klopp and J. Kravic and K. Krjut{\v s}kov and C. Langford and K. Leander and E. Lindholm and S. Lobbens and S. M{\"a}nnist{\"o} and G. Mirza and T.W. M{\"u}hleisen and B. Musk and M. Parkin and L. Rallidis and J. Saramies and B. Sennblad and S. Shah and G. Sigursson and A. Silveira and G. Steinbach and B. Thorand and J. Trakalo and F. Veglia and R. Wennauer and W. Winckler and D. Zabaneh and H. Campbell and {Van Duijn}, C. and A.G. Uitterlinden and A. Hofman and E. Sijbrands and G.R. Abecasis and K.R. Owen and E. Zeggini and M.D. Trip and N.G. Forouhi and A.-C. Syv{\"a}nen and J.G. Eriksson and L. Peltonen and M.M. N{\"o}then and B. Balkau and C.N.A. Palmer and V. Lyssenko and T. Tuomi and B. Isomaa and D.J. Hunter and L. Qi and A.R. Shuldiner and M. Roden and I. Barroso and T. Wilsgaard and John Beilby and K. Hovingh and J.F. Price and J.F. Wilson and R. Rauramaa and T.A. Lakka and L. Lind and G. Dedoussis and I. Nj{\o}lstad and N.L. Pedersen and K.-T. Khaw and N.J. Wareham and S.M. Keinanen-Kiukaanniemi and T.E. Saaristo and E. Korpi-Hy{\"o}v{\"a}lti and J. Saltevo and M. Laakso and J. Kuusisto and A. Metspalu and F.S. Collins and K.L. Mohlke and R.N. Bergman and J. Tuomilehto and B.O. Boehm and C. Gieger and K. Hveem and S. Cauchi and P. Froguel and D. Baldassarre and E. Tremoli and S.E. Humphries and D. Saleheen and J. Danesh and E. Ingelsson and S. Ripatti and V. Salomaa and R. Erbel and K.-H. J{\"o}ckel and S. Moebus and A. Peters and T. Illig and U.D. Faire and A. Hamsten and A.D. Morris and P.J. Donnelly and T.M. Frayling and A.T. Hattersley and E. Boerwinkle and O. Melander and S. Kathiresan and P.M. Nilsson and P. Deloukas and U. Thorsteinsdottir and L.C. Groop and K. Stefansson and F. Hu and J.S. Pankow and J. Dupuis and J.B. Meigs and D. Altshuler and M. Boehnke and M.I. Mccarthy",

year = "2012",

month = sep,

day = "1",

doi = "10.1038/ng.2383",

language = "English",

volume = "44",

pages = "981--92",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

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}

Morris, AP, Voight, BF, Teslovich, TM, Ferreira, T, Segrè, AV, Steinthorsdottir, V, Strawbridge, RJ, Khan, H, Grallert, H, Mahajan, A, Prokopenko, I, Kang, HM, Dina, C, Esko, T, Fraser, RM, Kanoni, S, Kumar, A, Lagou, V, Langenberg, C, Luan, J, Lindgren, CM, Müller-Nurasyid, M, Pechlivanis, S, Rayner, NW, Scott, LJ, Wiltshire, S, Yengo, L, Kinnunen, L, Rossin, EJ, Raychaudhuri, S, Johnson, AD, Dimas, AS, Loos, RJF, Vedantam, S, Chen, H, Florez, JC, Fox, C, Liu, C-T, Rybin, D, Couper, DJ, Kao, WHL, Li, M, Cornelis, MC, Kraft, P, Sun, Q, Van Dam, RM, Stringham, HM, Chines, PS, Fischer, K, Fontanillas, P, Holmen, OL, Hunt, SE, Jackson, AU, Kong, A, Lawrence, R, Meyer, J, Perry, JRB, Platou, CGP, Potter, S, Rehnberg, E, Robertson, N, Sivapalaratnam, S, Stančáková, A, Stirrups, K, Thorleifsson, G, Tikkanen, E, Wood, AR, Almgren, P, Atalay, M, Benediktsson, R, Bonnycastle, LL, Burtt, N, Carey, J, Charpentier, G, Crenshaw, AT, Doney, ASF, Dorkhan, M, Edkins, S, Emilsson, V, Eury, E, Forsen, T, Gertow, K, Gigante, B, Grant, GB, Groves, CJ, Guiducci, C, Herder, C, Hreidarsson, AB, Hui, J , James, A, Jonsson, A, Rathmann, W, Klopp, N, Kravic, J, Krjutškov, K, Langford, C, Leander, K, Lindholm, E, Lobbens, S, Männistö, S, Mirza, G, Mühleisen, TW, Musk, B, Parkin, M, Rallidis, L, Saramies, J, Sennblad, B, Shah, S, Sigursson, G, Silveira, A, Steinbach, G, Thorand, B, Trakalo, J, Veglia, F, Wennauer, R, Winckler, W, Zabaneh, D, Campbell, H, Van Duijn, C, Uitterlinden, AG, Hofman, A, Sijbrands, E, Abecasis, GR, Owen, KR, Zeggini, E, Trip, MD, Forouhi, NG, Syvänen, A-C, Eriksson, JG, Peltonen, L, Nöthen, MM, Balkau, B, Palmer, CNA, Lyssenko, V, Tuomi, T, Isomaa, B, Hunter, DJ, Qi, L, Shuldiner, AR, Roden, M, Barroso, I, Wilsgaard, T, Beilby, J, Hovingh, K, Price, JF, Wilson, JF, Rauramaa, R, Lakka, TA, Lind, L, Dedoussis, G, Njølstad, I, Pedersen, NL, Khaw, K-T, Wareham, NJ, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Korpi-Hyövälti, E, Saltevo, J, Laakso, M, Kuusisto, J, Metspalu, A, Collins, FS, Mohlke, KL, Bergman, RN, Tuomilehto, J, Boehm, BO, Gieger, C, Hveem, K, Cauchi, S, Froguel, P, Baldassarre, D, Tremoli, E, Humphries, SE, Saleheen, D, Danesh, J, Ingelsson, E, Ripatti, S, Salomaa, V, Erbel, R, Jöckel, K-H, Moebus, S, Peters, A, Illig, T, Faire, UD, Hamsten, A, Morris, AD, Donnelly, PJ, Frayling, TM, Hattersley, AT, Boerwinkle, E, Melander, O, Kathiresan, S, Nilsson, PM, Deloukas, P, Thorsteinsdottir, U, Groop, LC, Stefansson, K, Hu, F, Pankow, JS, Dupuis, J, Meigs, JB, Altshuler, D, Boehnke, M & Mccarthy, MI 2012, 'Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes', Nature Genetics, vol. 44, no. 9, pp. 981-92. https://doi.org/10.1038/ng.2383

TY - JOUR

T1 - Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

AU - Morris, A.P.

AU - Voight, B.F.

AU - Teslovich, T.M.

AU - Ferreira, T.

AU - Segrè, A.V.

AU - Steinthorsdottir, V.

AU - Strawbridge, R.J.

AU - Khan, H.

AU - Grallert, H.

AU - Mahajan, A.

AU - Prokopenko, I.

AU - Kang, H.M.

AU - Dina, C.

AU - Esko, T.

AU - Fraser, R.M.

AU - Kanoni, S.

AU - Kumar, A.

AU - Lagou, V.

AU - Langenberg, C.

AU - Luan, J.

AU - Lindgren, C.M.

AU - Müller-Nurasyid, M.

AU - Pechlivanis, S.

AU - Rayner, N.W.

AU - Scott, L.J.

AU - Wiltshire, S.

AU - Yengo, L.

AU - Kinnunen, L.

AU - Rossin, E.J.

AU - Raychaudhuri, S.

AU - Johnson, A.D.

AU - Dimas, A.S.

AU - Loos, R.J.F.

AU - Vedantam, S.

AU - Chen, H.

AU - Florez, J.C.

AU - Fox, C.

AU - Liu, C.-T.

AU - Rybin, D.

AU - Couper, D.J.

AU - Kao, W.H.L.

AU - Li, M.

AU - Cornelis, M.C.

AU - Kraft, P.

AU - Sun, Q.

AU - Van Dam, R.M.

AU - Stringham, H.M.

AU - Chines, P.S.

AU - Fischer, K.

AU - Fontanillas, P.

AU - Holmen, O.L.

AU - Hunt, S.E.

AU - Jackson, A.U.

AU - Kong, A.

AU - Lawrence, Robert

AU - Meyer, J.

AU - Perry, J.R.B.

AU - Platou, C.G.P.

AU - Potter, S.

AU - Rehnberg, E.

AU - Robertson, N.

AU - Sivapalaratnam, S.

AU - Stančáková, A.

AU - Stirrups, K.

AU - Thorleifsson, G.

AU - Tikkanen, E.

AU - Wood, A.R.

AU - Almgren, P.

AU - Atalay, M.

AU - Benediktsson, R.

AU - Bonnycastle, L.L.

AU - Burtt, N.

AU - Carey, J.

AU - Charpentier, G.

AU - Crenshaw, A.T.

AU - Doney, A.S.F.

AU - Dorkhan, M.

AU - Edkins, S.

AU - Emilsson, V.

AU - Eury, E.

AU - Forsen, T.

AU - Gertow, K.

AU - Gigante, B.

AU - Grant, G.B.

AU - Groves, C.J.

AU - Guiducci, C.

AU - Herder, C.

AU - Hreidarsson, A.B.

AU - Hui, Jennie

AU - James, Alan

AU - Jonsson, A.

AU - Rathmann, W.

AU - Klopp, N.

AU - Kravic, J.

AU - Krjutškov, K.

AU - Langford, C.

AU - Leander, K.

AU - Lindholm, E.

AU - Lobbens, S.

AU - Männistö, S.

AU - Mirza, G.

AU - Mühleisen, T.W.

AU - Musk, B.

AU - Parkin, M.

AU - Rallidis, L.

AU - Saramies, J.

AU - Sennblad, B.

AU - Shah, S.

AU - Sigursson, G.

AU - Silveira, A.

AU - Steinbach, G.

AU - Thorand, B.

AU - Trakalo, J.

AU - Veglia, F.

AU - Wennauer, R.

AU - Winckler, W.

AU - Zabaneh, D.

AU - Campbell, H.

AU - Van Duijn, C.

AU - Uitterlinden, A.G.

AU - Hofman, A.

AU - Sijbrands, E.

AU - Abecasis, G.R.

AU - Owen, K.R.

AU - Zeggini, E.

AU - Trip, M.D.

AU - Forouhi, N.G.

AU - Syvänen, A.-C.

AU - Eriksson, J.G.

AU - Peltonen, L.

AU - Nöthen, M.M.

AU - Balkau, B.

AU - Palmer, C.N.A.

AU - Lyssenko, V.

AU - Tuomi, T.

AU - Isomaa, B.

AU - Hunter, D.J.

AU - Qi, L.

AU - Shuldiner, A.R.

AU - Roden, M.

AU - Barroso, I.

AU - Wilsgaard, T.

AU - Beilby, John

AU - Hovingh, K.

AU - Price, J.F.

AU - Wilson, J.F.

AU - Rauramaa, R.

AU - Lakka, T.A.

AU - Lind, L.

AU - Dedoussis, G.

AU - Njølstad, I.

AU - Pedersen, N.L.

AU - Khaw, K.-T.

AU - Wareham, N.J.

AU - Keinanen-Kiukaanniemi, S.M.

AU - Saaristo, T.E.

AU - Korpi-Hyövälti, E.

AU - Saltevo, J.

AU - Laakso, M.

AU - Kuusisto, J.

AU - Metspalu, A.

AU - Collins, F.S.

AU - Mohlke, K.L.

AU - Bergman, R.N.

AU - Tuomilehto, J.

AU - Boehm, B.O.

AU - Gieger, C.

AU - Hveem, K.

AU - Cauchi, S.

AU - Froguel, P.

AU - Baldassarre, D.

AU - Tremoli, E.

AU - Humphries, S.E.

AU - Saleheen, D.

AU - Danesh, J.

AU - Ingelsson, E.

AU - Ripatti, S.

AU - Salomaa, V.

AU - Erbel, R.

AU - Jöckel, K.-H.

AU - Moebus, S.

AU - Peters, A.

AU - Illig, T.

AU - Faire, U.D.

AU - Hamsten, A.

AU - Morris, A.D.

AU - Donnelly, P.J.

AU - Frayling, T.M.

AU - Hattersley, A.T.

AU - Boerwinkle, E.

AU - Melander, O.

AU - Kathiresan, S.

AU - Nilsson, P.M.

AU - Deloukas, P.

AU - Thorsteinsdottir, U.

AU - Groop, L.C.

AU - Stefansson, K.

AU - Hu, F.

AU - Pankow, J.S.

AU - Dupuis, J.

AU - Meigs, J.B.

AU - Altshuler, D.

AU - Boehnke, M.

AU - Mccarthy, M.I.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

AB - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

U2 - 10.1038/ng.2383

DO - 10.1038/ng.2383

M3 - Article

C2 - 22885922

SN - 1061-4036

VL - 44

SP - 981

EP - 992

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Abstract

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