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

AP Morris; BF Voight; TM Teslovich; T Ferreira; AV Segre; V Steinthorsdottir; RJ Strawbridge; H Khan; H Grallert; A Mahajan; I Prokopenko; HM Kang; C Dina; T Esko; RM Fraser; S Kanoni; A Kumar; V Lagou; C Langenberg; JA Luan; CM Lindgren; M Muller-Nurasyid; S Pechlivanis; NW Rayner; LJ Scott; S Wiltshire; L Yengo; L Kinnunen; EJ Rossin; S Raychaudhuri; AD Johnson; AS Dimas; RJF Loos; S Vedantam; H Chen; JC Florez; C Fox; CT Liu; D Rybin; DJ Couper; WHL Kao; M Li; MC Cornelis; P Kraft; Q Sun; RM van Dam; HM Stringham; PS Chines; K (Kirsten) Fischer; P Fontanillas; OL Holmen; SE Hunt; AU Jackson; A Kong; R Lawrence; J Meyer; JRB Perry; CGP Platou; S Potter; E Rehnberg; N Robertson; S Sivapalaratnam; A Stancakova; K Stirrups; G Thorleifsson; E Tikkanen; AR Wood; P Almgren; M Atalay; R Benediktsson; LL Bonnycastle; N Burtt; J Carey; G Charpentier; AT Crenshaw; ASF Doney; M Dorkhan; S Edkins; V Emilsson; E Eury; T Forsen; K Gertow; B Gigante; GB Grant; CJ Groves; C Guiducci; Cindy Herder; AB Hreidarsson; JN Hui; A James; A Jonsson; W Rathmann; N Klopp; J Kravic; K Krjutskov; C Langford; K Leander; E Lindholm; S Lobbens; S Mannisto; G Mirza; TW Muhleisen; B Musk; M Parkin; L Rallidis; J Saramies; B Sennblad; S Shah; G Sigurdsson; A Silveira; G Steinbach; B Thorand; J Trakalo; F Veglia; R Wennauer; W Winckler; D Zabaneh; H Campbell; Cornelia Duijn; André Uitterlinden; Bert Hofman; E.J.G. Sijbrands; GR Abecasis; KR Owen; E Zeggini; MD Trip; NG Forouhi; AC Syvanen; JG Eriksson; L Peltonen; MM Nothen; B Balkau; CNA Palmer; V Lyssenko; T Tuomi; B Isomaa; DJ Hunter; L Qi; AR Shuldiner; M Roden; I Barroso; T Wilsgaard; J Beilby; K Hovingh; JF Price; JF Wilson; R Rauramaa; TA Lakka; L Lind; G Dedoussis; I Njolstad; NL Pedersen; KT Khaw; NJ Wareham; SM Keinanen-Kiukaanniemi; TE Saaristo; E Korpi-Hyovalti; J Saltevo; M Laakso; J Kuusisto; A Metspalu; FS Collins; KL Mohlke; RN Bergman; J Tuomilehto; BO Boehm; C Gieger; K Hveem; S Cauchi; P Froguel; D Baldassarre; E Tremoli; SE Humphries; D Saleheen; J Danesh; E Ingelsson; S Ripatti; V Salomaa; R Erbel; KH Jockel; S Moebus; A Peters; T Illig; U de Faire; A Hamsten; AD Morris; PJ Donnelly; TM Frayling; AT Hattersley; E Boerwinkle; O Melander; S Kathiresan; PM Nilsson; P Deloukas; U Thorsteinsdottir; LC Groop; K Stefansson; F Hu; JS Pankow; J Dupuis; JB Meigs; D Altshuler; M Boehnke; MI McCarthy

doi:10.1038/ng.2383

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

AP Morris, BF Voight, TM Teslovich, T Ferreira, AV Segre, V Steinthorsdottir, RJ Strawbridge, H Khan, H Grallert, A Mahajan, I Prokopenko, HM Kang, C Dina, T Esko, RM Fraser, S Kanoni, A Kumar, V Lagou, C Langenberg, JA LuanCM Lindgren, M Muller-Nurasyid, S Pechlivanis, NW Rayner, LJ Scott, S Wiltshire, L Yengo, L Kinnunen, EJ Rossin, S Raychaudhuri, AD Johnson, AS Dimas, RJF Loos, S Vedantam, H Chen, JC Florez, C Fox, CT Liu, D Rybin, DJ Couper, WHL Kao, M Li, MC Cornelis, P Kraft, Q Sun, RM van Dam, HM Stringham, PS Chines, K (Kirsten) Fischer, P Fontanillas, OL Holmen, SE Hunt, AU Jackson, A Kong, R Lawrence, J Meyer, JRB Perry, CGP Platou, S Potter, E Rehnberg, N Robertson, S Sivapalaratnam, A Stancakova, K Stirrups, G Thorleifsson, E Tikkanen, AR Wood, P Almgren, M Atalay, R Benediktsson, LL Bonnycastle, N Burtt, J Carey, G Charpentier, AT Crenshaw, ASF Doney, M Dorkhan, S Edkins, V Emilsson, E Eury, T Forsen, K Gertow, B Gigante, GB Grant, CJ Groves, C Guiducci, Cindy Herder, AB Hreidarsson, JN Hui, A James, A Jonsson, W Rathmann, N Klopp, J Kravic, K Krjutskov, C Langford, K Leander, E Lindholm, S Lobbens, S Mannisto, G Mirza, TW Muhleisen, B Musk, M Parkin, L Rallidis, J Saramies, B Sennblad, S Shah, G Sigurdsson, A Silveira, G Steinbach, B Thorand, J Trakalo, F Veglia, R Wennauer, W Winckler, D Zabaneh, H Campbell, Cornelia Duijn, André Uitterlinden, Bert Hofman, E.J.G. Sijbrands, GR Abecasis, KR Owen, E Zeggini, MD Trip, NG Forouhi, AC Syvanen, JG Eriksson, L Peltonen, MM Nothen, B Balkau, CNA Palmer, V Lyssenko, T Tuomi, B Isomaa, DJ Hunter, L Qi, AR Shuldiner, M Roden, I Barroso, T Wilsgaard, J Beilby, K Hovingh, JF Price, JF Wilson, R Rauramaa, TA Lakka, L Lind, G Dedoussis, I Njolstad, NL Pedersen, KT Khaw, NJ Wareham, SM Keinanen-Kiukaanniemi, TE Saaristo, E Korpi-Hyovalti, J Saltevo, M Laakso, J Kuusisto, A Metspalu, FS Collins, KL Mohlke, RN Bergman, J Tuomilehto, BO Boehm, C Gieger, K Hveem, S Cauchi, P Froguel, D Baldassarre, E Tremoli, SE Humphries, D Saleheen, J Danesh, E Ingelsson, S Ripatti, V Salomaa, R Erbel, KH Jockel, S Moebus, A Peters, T Illig, U de Faire, A Hamsten, AD Morris, PJ Donnelly, TM Frayling, AT Hattersley, E Boerwinkle, O Melander, S Kathiresan, PM Nilsson, P Deloukas, U Thorsteinsdottir, LC Groop, K Stefansson, F Hu, JS Pankow, J Dupuis, JB Meigs, D Altshuler, M Boehnke, MI McCarthy

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

1410 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. Genomewide 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	Undefined/Unknown
Pages (from-to)	981-+
Journal	Nature Genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2383
Publication status	Published - 2012

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

Access to Document

10.1038/ng.2383

http://hdl.handle.net/1765/58733

Cite this

Morris, AP., Voight, BF., Teslovich, TM., Ferreira, T., Segre, 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., ... McCarthy, MI. (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-+. https://doi.org/10.1038/ng.2383

@article{119b80dd80444e0dad3995a306317ad6,

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. Genomewide 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 = "AP Morris and BF Voight and TM Teslovich and T Ferreira and AV Segre and V Steinthorsdottir and RJ Strawbridge and H Khan and H Grallert and A Mahajan and I Prokopenko and HM Kang and C Dina and T Esko and RM Fraser and S Kanoni and A Kumar and V Lagou and C Langenberg and JA Luan and CM Lindgren and M Muller-Nurasyid and S Pechlivanis and NW Rayner and LJ Scott and S Wiltshire and L Yengo and L Kinnunen and EJ Rossin and S Raychaudhuri and AD Johnson and AS Dimas and RJF Loos and S Vedantam and H Chen and JC Florez and C Fox and CT Liu and D Rybin and DJ Couper and WHL Kao and M Li and MC Cornelis and P Kraft and Q Sun and {van Dam}, RM and HM Stringham and PS Chines and Fischer, {K (Kirsten)} and P Fontanillas and OL Holmen and SE Hunt and AU Jackson and A Kong and R Lawrence and J Meyer and JRB Perry and CGP Platou and S Potter and E Rehnberg and N Robertson and S Sivapalaratnam and A Stancakova and K Stirrups and G Thorleifsson and E Tikkanen and AR Wood and P Almgren and M Atalay and R Benediktsson and LL Bonnycastle and N Burtt and J Carey and G Charpentier and AT Crenshaw and ASF Doney and M Dorkhan and S Edkins and V Emilsson and E Eury and T Forsen and K Gertow and B Gigante and GB Grant and CJ Groves and C Guiducci and Cindy Herder and AB Hreidarsson and JN Hui and A James and A Jonsson and W Rathmann and N Klopp and J Kravic and K Krjutskov and C Langford and K Leander and E Lindholm and S Lobbens and S Mannisto and G Mirza and TW Muhleisen and B Musk and M Parkin and L Rallidis and J Saramies and B Sennblad and S Shah and G Sigurdsson 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 Cornelia Duijn and Andr{\'e} Uitterlinden and Bert Hofman and E.J.G. Sijbrands and GR Abecasis and KR Owen and E Zeggini and MD Trip and NG Forouhi and AC Syvanen and JG Eriksson and L Peltonen and MM Nothen and B Balkau and CNA Palmer and V Lyssenko and T Tuomi and B Isomaa and DJ Hunter and L Qi and AR Shuldiner and M Roden and I Barroso and T Wilsgaard and J Beilby and K Hovingh and JF Price and JF Wilson and R Rauramaa and TA Lakka and L Lind and G Dedoussis and I Njolstad and NL Pedersen and KT Khaw and NJ Wareham and SM Keinanen-Kiukaanniemi and TE Saaristo and E Korpi-Hyovalti and J Saltevo and M Laakso and J Kuusisto and A Metspalu and FS Collins and KL Mohlke and RN Bergman and J Tuomilehto and BO Boehm and C Gieger and K Hveem and S Cauchi and P Froguel and D Baldassarre and E Tremoli and SE Humphries and D Saleheen and J Danesh and E Ingelsson and S Ripatti and V Salomaa and R Erbel and KH Jockel and S Moebus and A Peters and T Illig and {de Faire}, U and A Hamsten and AD Morris and PJ Donnelly and TM Frayling and AT Hattersley and E Boerwinkle and O Melander and S Kathiresan and PM Nilsson and P Deloukas and U Thorsteinsdottir and LC Groop and K Stefansson and F Hu and JS Pankow and J Dupuis and JB Meigs and D Altshuler and M Boehnke and MI McCarthy",

year = "2012",

doi = "10.1038/ng.2383",

language = "Undefined/Unknown",

volume = "44",

pages = "981--+",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

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Morris, AP, Voight, BF, Teslovich, TM, Ferreira, T, Segre, 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, JA, Lindgren, CM, Muller-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, CT, 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, Stancakova, 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, JN, James, A, Jonsson, A, Rathmann, W, Klopp, N, Kravic, J, Krjutskov, K, Langford, C, Leander, K, Lindholm, E, Lobbens, S, Mannisto, S, Mirza, G, Muhleisen, TW, Musk, B, Parkin, M, Rallidis, L, Saramies, J, Sennblad, B, Shah, S, Sigurdsson, G, Silveira, A, Steinbach, G, Thorand, B, Trakalo, J, Veglia, F, Wennauer, R, Winckler, W, Zabaneh, D, Campbell, H, Duijn, C, Uitterlinden, A , Hofman, B , Sijbrands, EJG, Abecasis, GR, Owen, KR, Zeggini, E, Trip, MD, Forouhi, NG, Syvanen, AC, Eriksson, JG, Peltonen, L, Nothen, 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, Njolstad, I, Pedersen, NL, Khaw, KT, Wareham, NJ, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Korpi-Hyovalti, 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, Jockel, KH, Moebus, S, Peters, A, Illig, T, de Faire, U, 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-+. 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, AP

AU - Voight, BF

AU - Teslovich, TM

AU - Ferreira, T

AU - Segre, AV

AU - Steinthorsdottir, V

AU - Strawbridge, RJ

AU - Khan, H

AU - Grallert, H

AU - Mahajan, A

AU - Prokopenko, I

AU - Kang, HM

AU - Dina, C

AU - Esko, T

AU - Fraser, RM

AU - Kanoni, S

AU - Kumar, A

AU - Lagou, V

AU - Langenberg, C

AU - Luan, JA

AU - Lindgren, CM

AU - Muller-Nurasyid, M

AU - Pechlivanis, S

AU - Rayner, NW

AU - Scott, LJ

AU - Wiltshire, S

AU - Yengo, L

AU - Kinnunen, L

AU - Rossin, EJ

AU - Raychaudhuri, S

AU - Johnson, AD

AU - Dimas, AS

AU - Loos, RJF

AU - Vedantam, S

AU - Chen, H

AU - Florez, JC

AU - Fox, C

AU - Liu, CT

AU - Rybin, D

AU - Couper, DJ

AU - Kao, WHL

AU - Li, M

AU - Cornelis, MC

AU - Kraft, P

AU - Sun, Q

AU - van Dam, RM

AU - Stringham, HM

AU - Chines, PS

AU - Fischer, K (Kirsten)

AU - Fontanillas, P

AU - Holmen, OL

AU - Hunt, SE

AU - Jackson, AU

AU - Kong, A

AU - Lawrence, R

AU - Meyer, J

AU - Perry, JRB

AU - Platou, CGP

AU - Potter, S

AU - Rehnberg, E

AU - Robertson, N

AU - Sivapalaratnam, S

AU - Stancakova, A

AU - Stirrups, K

AU - Thorleifsson, G

AU - Tikkanen, E

AU - Wood, AR

AU - Almgren, P

AU - Atalay, M

AU - Benediktsson, R

AU - Bonnycastle, LL

AU - Burtt, N

AU - Carey, J

AU - Charpentier, G

AU - Crenshaw, AT

AU - Doney, ASF

AU - Dorkhan, M

AU - Edkins, S

AU - Emilsson, V

AU - Eury, E

AU - Forsen, T

AU - Gertow, K

AU - Gigante, B

AU - Grant, GB

AU - Groves, CJ

AU - Guiducci, C

AU - Herder, Cindy

AU - Hreidarsson, AB

AU - Hui, JN

AU - James, A

AU - Jonsson, A

AU - Rathmann, W

AU - Klopp, N

AU - Kravic, J

AU - Krjutskov, K

AU - Langford, C

AU - Leander, K

AU - Lindholm, E

AU - Lobbens, S

AU - Mannisto, S

AU - Mirza, G

AU - Muhleisen, TW

AU - Musk, B

AU - Parkin, M

AU - Rallidis, L

AU - Saramies, J

AU - Sennblad, B

AU - Shah, S

AU - Sigurdsson, 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 - Duijn, Cornelia

AU - Uitterlinden, André

AU - Hofman, Bert

AU - Sijbrands, E.J.G.

AU - Abecasis, GR

AU - Owen, KR

AU - Zeggini, E

AU - Trip, MD

AU - Forouhi, NG

AU - Syvanen, AC

AU - Eriksson, JG

AU - Peltonen, L

AU - Nothen, MM

AU - Balkau, B

AU - Palmer, CNA

AU - Lyssenko, V

AU - Tuomi, T

AU - Isomaa, B

AU - Hunter, DJ

AU - Qi, L

AU - Shuldiner, AR

AU - Roden, M

AU - Barroso, I

AU - Wilsgaard, T

AU - Beilby, J

AU - Hovingh, K

AU - Price, JF

AU - Wilson, JF

AU - Rauramaa, R

AU - Lakka, TA

AU - Lind, L

AU - Dedoussis, G

AU - Njolstad, I

AU - Pedersen, NL

AU - Khaw, KT

AU - Wareham, NJ

AU - Keinanen-Kiukaanniemi, SM

AU - Saaristo, TE

AU - Korpi-Hyovalti, E

AU - Saltevo, J

AU - Laakso, M

AU - Kuusisto, J

AU - Metspalu, A

AU - Collins, FS

AU - Mohlke, KL

AU - Bergman, RN

AU - Tuomilehto, J

AU - Boehm, BO

AU - Gieger, C

AU - Hveem, K

AU - Cauchi, S

AU - Froguel, P

AU - Baldassarre, D

AU - Tremoli, E

AU - Humphries, SE

AU - Saleheen, D

AU - Danesh, J

AU - Ingelsson, E

AU - Ripatti, S

AU - Salomaa, V

AU - Erbel, R

AU - Jockel, KH

AU - Moebus, S

AU - Peters, A

AU - Illig, T

AU - de Faire, U

AU - Hamsten, A

AU - Morris, AD

AU - Donnelly, PJ

AU - Frayling, TM

AU - Hattersley, AT

AU - Boerwinkle, E

AU - Melander, O

AU - Kathiresan, S

AU - Nilsson, PM

AU - Deloukas, P

AU - Thorsteinsdottir, U

AU - Groop, LC

AU - Stefansson, K

AU - Hu, F

AU - Pankow, JS

AU - Dupuis, J

AU - Meigs, JB

AU - Altshuler, D

AU - Boehnke, M

AU - McCarthy, MI

PY - 2012

Y1 - 2012

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. Genomewide 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. Genomewide 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

SN - 1061-4036

VL - 44

SP - 981-+

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -