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

Andrew P. Morris, Benjamin F. Voight, Tanya M. Teslovich, Teresa Ferreira, Ayellet V. Segrè, Valgerdur Steinthorsdottir, Rona J. Strawbridge, Hassan Khan, Harald Grallert, Anubha Mahajan, Inga Prokopenko, Hyun Min Kang, Christian Dina, Tonu Esko, Ross M. Fraser, Stavroula Kanoni, Ashish Kumar, Vasiliki Lagou, Claudia Langenberg, Jian'An LuanCecilia M. Lindgren, Martina Müller-Nurasyid, Sonali Pechlivanis, N. William Rayner, Laura J. Scott, Steven Wiltshire, Loic Yengo, Leena Kinnunen, Elizabeth J. Rossin, Soumya Raychaudhuri, Andrew D. Johnson, Antigone S. Dimas, Ruth J F Loos, Sailaja Vedantam, Han Chen, Jose C. Florez, Caroline Fox, Ching Ti Liu, Denis Rybin, David J. Couper, Wen Hong L Kao, Man Li, Marilyn C. Cornelis, Peter Kraft, Qi Sun, Rob M. Van Dam, Heather M. Stringham, Peter S. Chines, Krista Fischer, Pierre Fontanillas, Oddgeir L. Holmen, Sarah E. Hunt, Anne U. Jackson, Augustine Kong, Robert Lawrence, Julia Meyer, John R B Perry, Carl G P Platou, Simon Potter, Emil Rehnberg, Neil Robertson, Suthesh Sivapalaratnam, Alena Stančáková, Kathleen Stirrups, Gudmar Thorleifsson, Emmi Tikkanen, Andrew R. Wood, Peter Almgren, Mustafa Atalay, Rafn Benediktsson, Lori L. Bonnycastle, Noël Burtt, Jason Carey, Guillaume Charpentier, Andrew T. Crenshaw, Alex S F Doney, Mozhgan Dorkhan, Sarah Edkins, Valur Emilsson, Elodie Eury, Tom Forsen, Karl Gertow, Bruna Gigante, George B. Grant, Christopher J. Groves, Candace Guiducci, Christian Herder, Astradur B. Hreidarsson, Jennie Hui, Alan James, Anna Jonsson, Wolfgang Rathmann, Norman Klopp, Jasmina Kravic, Kaarel Krjutškov, Cordelia Langford, Karin Leander, Eero Lindholm, Stéphane Lobbens, Satu MäNnistö, Ghazala Mirza, Thomas W. MüHleisen, Bill Musk, Melissa Parkin, Loukianos Rallidis, Jouko Saramies, Bengt Sennblad, Sonia Shah, Gunnar Sigursson, Angela Silveira, Gerald Steinbach, Barbara Thorand, Joseph Trakalo, Fabrizio Veglia, Roman Wennauer, Wendy Winckler, Delilah Zabaneh, Harry Campbell, Cornelia Van Duijn, Andre G. Uitterlinden, Albert Hofman, Eric Sijbrands, Goncalo R. Abecasis, Katharine R. Owen, Eleftheria Zeggini, Mieke D. Trip, Nita G. Forouhi, Ann Christine Syvänen, Johan G. Eriksson, Leena Peltonen, Markus M. Nöthen, Beverley Balkau, Colin N A Palmer, Valeriya Lyssenko, Tiinamaija Tuomi, Bo Isomaa, David J. Hunter, Lu Qi, Alan R. Shuldiner, Michael Roden, Ines Barroso, Tom Wilsgaard, John Beilby, Kees Hovingh, Jackie F. Price, James F. Wilson, Rainer Rauramaa, Timo A. Lakka, Lars Lind, George Dedoussis, Inger NjøLstad, Nancy L. Pedersen, Kay Tee Khaw, Nicholas J. Wareham, Sirkka M. Keinanen-Kiukaanniemi, Timo E. Saaristo, Eeva Korpi-HyöVäLti, Juha Saltevo, Markku Laakso, Johanna Kuusisto, Andres Metspalu, Francis S. Collins, Karen L. Mohlke, Richard N. Bergman, Jaakko Tuomilehto, Bernhard O. Boehm, Christian Gieger, Kristian Hveem, Stephane Cauchi, Philippe Froguel, Damiano Baldassarre, Elena Tremoli, Steve E. Humphries, Danish Saleheen, John Danesh, Erik Ingelsson, Samuli Ripatti, Veikko Salomaa, Raimund Erbel, Karl Heinz JöCkel, Susanne Moebus, Annette Peters, Thomas Illig, Ulf De Faire, Anders Hamsten, Andrew D. Morris, Peter J. Donnelly, Timothy M. Frayling, Andrew T. Hattersley, Eric Boerwinkle, Olle Melander, Sekar Kathiresan, Peter M. Nilsson, Panos Deloukas, Unnur Thorsteinsdottir, Leif C. Groop, Kari Stefansson, Frank Hu, James S. Pankow, Josée Dupuis, James B. Meigs, David Altshuler, Michael Boehnke, Mark I. McCarthy

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)981-990
Number of pages10
JournalNature Genetics
Volume44
Issue number9
DOIs
StatePublished - Sep 2012

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Type 2 Diabetes Mellitus
Adipokines
Meta-Analysis
Molecular Biology
Cell Cycle
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., ... McCarthy, M. I. (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-990. https://doi.org/10.1038/ng.2383

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. / Morris, Andrew P.; Voight, Benjamin F.; Teslovich, Tanya M.; Ferreira, Teresa; Segrè, Ayellet V.; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Khan, Hassan; Grallert, Harald; Mahajan, Anubha; Prokopenko, Inga; Kang, Hyun Min; Dina, Christian; Esko, Tonu; Fraser, Ross M.; Kanoni, Stavroula; Kumar, Ashish; Lagou, Vasiliki; Langenberg, Claudia; Luan, Jian'An; Lindgren, Cecilia M.; Müller-Nurasyid, Martina; Pechlivanis, Sonali; Rayner, N. William; Scott, Laura J.; Wiltshire, Steven; Yengo, Loic; Kinnunen, Leena; Rossin, Elizabeth J.; Raychaudhuri, Soumya; Johnson, Andrew D.; Dimas, Antigone S.; Loos, Ruth J F; Vedantam, Sailaja; Chen, Han; Florez, Jose C.; Fox, Caroline; Liu, Ching Ti; Rybin, Denis; Couper, David J.; Kao, Wen Hong L; Li, Man; Cornelis, Marilyn C.; Kraft, Peter; Sun, Qi; Van Dam, Rob M.; Stringham, Heather M.; Chines, Peter S.; Fischer, Krista; Fontanillas, Pierre; Holmen, Oddgeir L.; Hunt, Sarah E.; Jackson, Anne U.; Kong, Augustine; Lawrence, Robert; Meyer, Julia; Perry, John R B; Platou, Carl G P; Potter, Simon; Rehnberg, Emil; Robertson, Neil; Sivapalaratnam, Suthesh; Stančáková, Alena; Stirrups, Kathleen; Thorleifsson, Gudmar; Tikkanen, Emmi; Wood, Andrew R.; Almgren, Peter; Atalay, Mustafa; Benediktsson, Rafn; Bonnycastle, Lori L.; Burtt, Noël; Carey, Jason; Charpentier, Guillaume; Crenshaw, Andrew T.; Doney, Alex S F; Dorkhan, Mozhgan; Edkins, Sarah; Emilsson, Valur; Eury, Elodie; Forsen, Tom; Gertow, Karl; Gigante, Bruna; Grant, George B.; Groves, Christopher J.; Guiducci, Candace; Herder, Christian; Hreidarsson, Astradur B.; Hui, Jennie; James, Alan; Jonsson, Anna; Rathmann, Wolfgang; Klopp, Norman; Kravic, Jasmina; Krjutškov, Kaarel; Langford, Cordelia; Leander, Karin; Lindholm, Eero; Lobbens, Stéphane; MäNnistö, Satu; Mirza, Ghazala; MüHleisen, Thomas W.; Musk, Bill; Parkin, Melissa; Rallidis, Loukianos; Saramies, Jouko; Sennblad, Bengt; Shah, Sonia; Sigursson, Gunnar; Silveira, Angela; Steinbach, Gerald; Thorand, Barbara; Trakalo, Joseph; Veglia, Fabrizio; Wennauer, Roman; Winckler, Wendy; Zabaneh, Delilah; Campbell, Harry; Van Duijn, Cornelia; Uitterlinden, Andre G.; Hofman, Albert; Sijbrands, Eric; Abecasis, Goncalo R.; Owen, Katharine R.; Zeggini, Eleftheria; Trip, Mieke D.; Forouhi, Nita G.; Syvänen, Ann Christine; Eriksson, Johan G.; Peltonen, Leena; Nöthen, Markus M.; Balkau, Beverley; Palmer, Colin N A; Lyssenko, Valeriya; Tuomi, Tiinamaija; Isomaa, Bo; Hunter, David J.; Qi, Lu; Shuldiner, Alan R.; Roden, Michael; Barroso, Ines; Wilsgaard, Tom; Beilby, John; Hovingh, Kees; Price, Jackie F.; Wilson, James F.; Rauramaa, Rainer; Lakka, Timo A.; Lind, Lars; Dedoussis, George; NjøLstad, Inger; Pedersen, Nancy L.; Khaw, Kay Tee; Wareham, Nicholas J.; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Korpi-HyöVäLti, Eeva; Saltevo, Juha; Laakso, Markku; Kuusisto, Johanna; Metspalu, Andres; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Tuomilehto, Jaakko; Boehm, Bernhard O.; Gieger, Christian; Hveem, Kristian; Cauchi, Stephane; Froguel, Philippe; Baldassarre, Damiano; Tremoli, Elena; Humphries, Steve E.; Saleheen, Danish; Danesh, John; Ingelsson, Erik; Ripatti, Samuli; Salomaa, Veikko; Erbel, Raimund; JöCkel, Karl Heinz; Moebus, Susanne; Peters, Annette; Illig, Thomas; Faire, Ulf De; Hamsten, Anders; Morris, Andrew D.; Donnelly, Peter J.; Frayling, Timothy M.; Hattersley, Andrew T.; Boerwinkle, Eric; Melander, Olle; Kathiresan, Sekar; Nilsson, Peter M.; Deloukas, Panos; Thorsteinsdottir, Unnur; Groop, Leif C.; Stefansson, Kari; Hu, Frank; Pankow, James S.; Dupuis, Josée; Meigs, James B.; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.

In: Nature Genetics, Vol. 44, No. 9, 09.2012, p. 981-990.

Research output: Contribution to journalArticle

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, JA, 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, 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, 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, AC, 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, KT, 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, KH, 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. 981-990. https://doi.org/10.1038/ng.2383
Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics. 2012 Sep;44(9):981-990. https://doi.org/10.1038/ng.2383
Morris, Andrew P. ; Voight, Benjamin F. ; Teslovich, Tanya M. ; Ferreira, Teresa ; Segrè, Ayellet V. ; Steinthorsdottir, Valgerdur ; Strawbridge, Rona J. ; Khan, Hassan ; Grallert, Harald ; Mahajan, Anubha ; Prokopenko, Inga ; Kang, Hyun Min ; Dina, Christian ; Esko, Tonu ; Fraser, Ross M. ; Kanoni, Stavroula ; Kumar, Ashish ; Lagou, Vasiliki ; Langenberg, Claudia ; Luan, Jian'An ; Lindgren, Cecilia M. ; Müller-Nurasyid, Martina ; Pechlivanis, Sonali ; Rayner, N. William ; Scott, Laura J. ; Wiltshire, Steven ; Yengo, Loic ; Kinnunen, Leena ; Rossin, Elizabeth J. ; Raychaudhuri, Soumya ; Johnson, Andrew D. ; Dimas, Antigone S. ; Loos, Ruth J F ; Vedantam, Sailaja ; Chen, Han ; Florez, Jose C. ; Fox, Caroline ; Liu, Ching Ti ; Rybin, Denis ; Couper, David J. ; Kao, Wen Hong L ; Li, Man ; Cornelis, Marilyn C. ; Kraft, Peter ; Sun, Qi ; Van Dam, Rob M. ; Stringham, Heather M. ; Chines, Peter S. ; Fischer, Krista ; Fontanillas, Pierre ; Holmen, Oddgeir L. ; Hunt, Sarah E. ; Jackson, Anne U. ; Kong, Augustine ; Lawrence, Robert ; Meyer, Julia ; Perry, John R B ; Platou, Carl G P ; Potter, Simon ; Rehnberg, Emil ; Robertson, Neil ; Sivapalaratnam, Suthesh ; Stančáková, Alena ; Stirrups, Kathleen ; Thorleifsson, Gudmar ; Tikkanen, Emmi ; Wood, Andrew R. ; Almgren, Peter ; Atalay, Mustafa ; Benediktsson, Rafn ; Bonnycastle, Lori L. ; Burtt, Noël ; Carey, Jason ; Charpentier, Guillaume ; Crenshaw, Andrew T. ; Doney, Alex S F ; Dorkhan, Mozhgan ; Edkins, Sarah ; Emilsson, Valur ; Eury, Elodie ; Forsen, Tom ; Gertow, Karl ; Gigante, Bruna ; Grant, George B. ; Groves, Christopher J. ; Guiducci, Candace ; Herder, Christian ; Hreidarsson, Astradur B. ; Hui, Jennie ; James, Alan ; Jonsson, Anna ; Rathmann, Wolfgang ; Klopp, Norman ; Kravic, Jasmina ; Krjutškov, Kaarel ; Langford, Cordelia ; Leander, Karin ; Lindholm, Eero ; Lobbens, Stéphane ; MäNnistö, Satu ; Mirza, Ghazala ; MüHleisen, Thomas W. ; Musk, Bill ; Parkin, Melissa ; Rallidis, Loukianos ; Saramies, Jouko ; Sennblad, Bengt ; Shah, Sonia ; Sigursson, Gunnar ; Silveira, Angela ; Steinbach, Gerald ; Thorand, Barbara ; Trakalo, Joseph ; Veglia, Fabrizio ; Wennauer, Roman ; Winckler, Wendy ; Zabaneh, Delilah ; Campbell, Harry ; Van Duijn, Cornelia ; Uitterlinden, Andre G. ; Hofman, Albert ; Sijbrands, Eric ; Abecasis, Goncalo R. ; Owen, Katharine R. ; Zeggini, Eleftheria ; Trip, Mieke D. ; Forouhi, Nita G. ; Syvänen, Ann Christine ; Eriksson, Johan G. ; Peltonen, Leena ; Nöthen, Markus M. ; Balkau, Beverley ; Palmer, Colin N A ; Lyssenko, Valeriya ; Tuomi, Tiinamaija ; Isomaa, Bo ; Hunter, David J. ; Qi, Lu ; Shuldiner, Alan R. ; Roden, Michael ; Barroso, Ines ; Wilsgaard, Tom ; Beilby, John ; Hovingh, Kees ; Price, Jackie F. ; Wilson, James F. ; Rauramaa, Rainer ; Lakka, Timo A. ; Lind, Lars ; Dedoussis, George ; NjøLstad, Inger ; Pedersen, Nancy L. ; Khaw, Kay Tee ; Wareham, Nicholas J. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Korpi-HyöVäLti, Eeva ; Saltevo, Juha ; Laakso, Markku ; Kuusisto, Johanna ; Metspalu, Andres ; Collins, Francis S. ; Mohlke, Karen L. ; Bergman, Richard N. ; Tuomilehto, Jaakko ; Boehm, Bernhard O. ; Gieger, Christian ; Hveem, Kristian ; Cauchi, Stephane ; Froguel, Philippe ; Baldassarre, Damiano ; Tremoli, Elena ; Humphries, Steve E. ; Saleheen, Danish ; Danesh, John ; Ingelsson, Erik ; Ripatti, Samuli ; Salomaa, Veikko ; Erbel, Raimund ; JöCkel, Karl Heinz ; Moebus, Susanne ; Peters, Annette ; Illig, Thomas ; Faire, Ulf De ; Hamsten, Anders ; Morris, Andrew D. ; Donnelly, Peter J. ; Frayling, Timothy M. ; Hattersley, Andrew T. ; Boerwinkle, Eric ; Melander, Olle ; Kathiresan, Sekar ; Nilsson, Peter M. ; Deloukas, Panos ; Thorsteinsdottir, Unnur ; Groop, Leif C. ; Stefansson, Kari ; Hu, Frank ; Pankow, James S. ; Dupuis, Josée ; Meigs, James B. ; Altshuler, David ; Boehnke, Michael ; McCarthy, Mark I. / Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. In: Nature Genetics. 2012 ; Vol. 44, No. 9. pp. 981-990.
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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 = "Morris, {Andrew P.} and Voight, {Benjamin F.} and Teslovich, {Tanya M.} and Teresa Ferreira and Segr{\`e}, {Ayellet V.} and Valgerdur Steinthorsdottir and Strawbridge, {Rona J.} and Hassan Khan and Harald Grallert and Anubha Mahajan and Inga Prokopenko and Kang, {Hyun Min} and Christian Dina and Tonu Esko and Fraser, {Ross M.} and Stavroula Kanoni and Ashish Kumar and Vasiliki Lagou and Claudia Langenberg and Jian'An Luan and Lindgren, {Cecilia M.} and Martina M{\"u}ller-Nurasyid and Sonali Pechlivanis and Rayner, {N. William} and Scott, {Laura J.} and Steven Wiltshire and Loic Yengo and Leena Kinnunen and Rossin, {Elizabeth J.} and Soumya Raychaudhuri and Johnson, {Andrew D.} and Dimas, {Antigone S.} and Loos, {Ruth J F} and Sailaja Vedantam and Han Chen and Florez, {Jose C.} and Caroline Fox and Liu, {Ching Ti} and Denis Rybin and Couper, {David J.} and Kao, {Wen Hong L} and Man Li and Cornelis, {Marilyn C.} and Peter Kraft and Qi Sun and {Van Dam}, {Rob M.} and Stringham, {Heather M.} and Chines, {Peter S.} and Krista Fischer and Pierre Fontanillas and Holmen, {Oddgeir L.} and Hunt, {Sarah E.} and Jackson, {Anne U.} and Augustine Kong and Robert Lawrence and Julia Meyer and Perry, {John R B} and Platou, {Carl G P} and Simon Potter and Emil Rehnberg and Neil Robertson and Suthesh Sivapalaratnam and Alena Stanč{\'a}kov{\'a} and Kathleen Stirrups and Gudmar Thorleifsson and Emmi Tikkanen and Wood, {Andrew R.} and Peter Almgren and Mustafa Atalay and Rafn Benediktsson and Bonnycastle, {Lori L.} and No{\"e}l Burtt and Jason Carey and Guillaume Charpentier and Crenshaw, {Andrew T.} and Doney, {Alex S F} and Mozhgan Dorkhan and Sarah Edkins and Valur Emilsson and Elodie Eury and Tom Forsen and Karl Gertow and Bruna Gigante and Grant, {George B.} and Groves, {Christopher J.} and Candace Guiducci and Christian Herder and Hreidarsson, {Astradur B.} and Jennie Hui and Alan James and Anna Jonsson and Wolfgang Rathmann and Norman Klopp and Jasmina Kravic and Kaarel Krjutškov and Cordelia Langford and Karin Leander and Eero Lindholm and St{\'e}phane Lobbens and Satu M{\"a}Nnist{\"o} and Ghazala Mirza and M{\"u}Hleisen, {Thomas W.} and Bill Musk and Melissa Parkin and Loukianos Rallidis and Jouko Saramies and Bengt Sennblad and Sonia Shah and Gunnar Sigursson and Angela Silveira and Gerald Steinbach and Barbara Thorand and Joseph Trakalo and Fabrizio Veglia and Roman Wennauer and Wendy Winckler and Delilah Zabaneh and Harry Campbell and {Van Duijn}, Cornelia and Uitterlinden, {Andre G.} and Albert Hofman and Eric Sijbrands and Abecasis, {Goncalo R.} and Owen, {Katharine R.} and Eleftheria Zeggini and Trip, {Mieke D.} and Forouhi, {Nita G.} and Syv{\"a}nen, {Ann Christine} and Eriksson, {Johan G.} and Leena Peltonen and N{\"o}then, {Markus M.} and Beverley Balkau and Palmer, {Colin N A} and Valeriya Lyssenko and Tiinamaija Tuomi and Bo Isomaa and Hunter, {David J.} and Lu Qi and Shuldiner, {Alan R.} and Michael Roden and Ines Barroso and Tom Wilsgaard and John Beilby and Kees Hovingh and Price, {Jackie F.} and Wilson, {James F.} and Rainer Rauramaa and Lakka, {Timo A.} and Lars Lind and George Dedoussis and Inger Nj{\o}Lstad and Pedersen, {Nancy L.} and Khaw, {Kay Tee} and Wareham, {Nicholas J.} and Keinanen-Kiukaanniemi, {Sirkka M.} and Saaristo, {Timo E.} and Eeva Korpi-Hy{\"o}V{\"a}Lti and Juha Saltevo and Markku Laakso and Johanna Kuusisto and Andres Metspalu and Collins, {Francis S.} and Mohlke, {Karen L.} and Bergman, {Richard N.} and Jaakko Tuomilehto and Boehm, {Bernhard O.} and Christian Gieger and Kristian Hveem and Stephane Cauchi and Philippe Froguel and Damiano Baldassarre and Elena Tremoli and Humphries, {Steve E.} and Danish Saleheen and John Danesh and Erik Ingelsson and Samuli Ripatti and Veikko Salomaa and Raimund Erbel and J{\"o}Ckel, {Karl Heinz} and Susanne Moebus and Annette Peters and Thomas Illig and Faire, {Ulf De} and Anders Hamsten and Morris, {Andrew D.} and Donnelly, {Peter J.} and Frayling, {Timothy M.} and Hattersley, {Andrew T.} and Eric Boerwinkle and Olle Melander and Sekar Kathiresan and Nilsson, {Peter M.} and Panos Deloukas and Unnur Thorsteinsdottir and Groop, {Leif C.} and Kari Stefansson and Frank Hu and Pankow, {James S.} and Jos{\'e}e Dupuis and Meigs, {James B.} and David Altshuler and Michael Boehnke and McCarthy, {Mark I.}",
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month = "9",
doi = "10.1038/ng.2383",
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pages = "981--990",
journal = "Nature Genetics",
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TY - JOUR

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

AU - Morris, Andrew P.

AU - Voight, Benjamin F.

AU - Teslovich, Tanya M.

AU - Ferreira, Teresa

AU - Segrè, Ayellet V.

AU - Steinthorsdottir, Valgerdur

AU - Strawbridge, Rona J.

AU - Khan, Hassan

AU - Grallert, Harald

AU - Mahajan, Anubha

AU - Prokopenko, Inga

AU - Kang, Hyun Min

AU - Dina, Christian

AU - Esko, Tonu

AU - Fraser, Ross M.

AU - Kanoni, Stavroula

AU - Kumar, Ashish

AU - Lagou, Vasiliki

AU - Langenberg, Claudia

AU - Luan, Jian'An

AU - Lindgren, Cecilia M.

AU - Müller-Nurasyid, Martina

AU - Pechlivanis, Sonali

AU - Rayner, N. William

AU - Scott, Laura J.

AU - Wiltshire, Steven

AU - Yengo, Loic

AU - Kinnunen, Leena

AU - Rossin, Elizabeth J.

AU - Raychaudhuri, Soumya

AU - Johnson, Andrew D.

AU - Dimas, Antigone S.

AU - Loos, Ruth J F

AU - Vedantam, Sailaja

AU - Chen, Han

AU - Florez, Jose C.

AU - Fox, Caroline

AU - Liu, Ching Ti

AU - Rybin, Denis

AU - Couper, David J.

AU - Kao, Wen Hong L

AU - Li, Man

AU - Cornelis, Marilyn C.

AU - Kraft, Peter

AU - Sun, Qi

AU - Van Dam, Rob M.

AU - Stringham, Heather M.

AU - Chines, Peter S.

AU - Fischer, Krista

AU - Fontanillas, Pierre

AU - Holmen, Oddgeir L.

AU - Hunt, Sarah E.

AU - Jackson, Anne U.

AU - Kong, Augustine

AU - Lawrence, Robert

AU - Meyer, Julia

AU - Perry, John R B

AU - Platou, Carl G P

AU - Potter, Simon

AU - Rehnberg, Emil

AU - Robertson, Neil

AU - Sivapalaratnam, Suthesh

AU - Stančáková, Alena

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PY - 2012/9

Y1 - 2012/9

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.

UR - http://www.scopus.com/inward/record.url?scp=84868337361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868337361&partnerID=8YFLogxK

U2 - 10.1038/ng.2383

DO - 10.1038/ng.2383

M3 - Article

C2 - 22885922

AN - SCOPUS:84868337361

VL - 44

SP - 981

EP - 990

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -