New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Josée Dupuis; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Nicole Soranzo; Anne U. Jackson; Eleanor Wheeler; Nicole L. Glazer; Nabila Bouatia-Naji; Ulf Gyllensten; Cecilia M. Lindgren; Reedik Mägi; Andrew P. Morris; Joshua Randall; Toby Johnson; Paul Elliott; Denis Rybin; Gudmar Thorleifsson; Valgerdur Steinthorsdottir; Peter Henneman; Harald Grallert; Abbas Dehghan; Jouke JanHottenga; Christopher S. Franklin; Pau Navarro; Kijoung Song; Anuj Goel; John R.B. Perry; Josephine M. Egan; Taina Lajunen; Niels Grarup; Thomas Sparsø; Alex Doney; Benjamin F. Voight; Heather M. Stringham; Man Li; Stavroula Kanoni; Peter Shrader; Christine Cavalcanti-Proença; Meena Kumari; Rafn Benediktsson; Nicholas J. Timpson; Christian Gieger; Carina Zabena; Ghislain Rocheleau; Erik Ingelsson; Ping An; Jeffrey O'Connell; Jian'An Luan; Amanda Elliott; Steven A. McCarroll; Felicity Payne; Rosa Maria Roccasecca; François Pattou; Praveen Sethupathy; Kristin Ardlie; Yavuz Ariyurek; Beverley Balkau; Philip Barter; John P. Beilby; Yoav Ben-Shlomo; Rafn Benediktsson; Amanda J. Bennett; Sven Bergmann; Murielle Bochud; Eric Boerwinkle; Amélie Bonnefond; Lori L. Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Suzannah J. Bumpstead; Guillaume Charpentier; Yii Der IdaChen; Peter Chines; Robert Clarke; Lachlan J. McOin; Matthew N. Cooper; Marilyn Cornelis; Gabe Crawford; Laura Crisponi; Ian N.M. Day; Eco J.C. De Geus; Jerome Delplanque; Christian Dina; Michael R. Erdos; Annette C. Fedson; Antje Fischer-Rosinsky; Nita G. Forouhi; Caroline S. Fox; Rune Frants; Maria GraziaFranzosi; Pilar Galan; Mark O. Goodarzi; Jürgen Graessler; Christopher J. Groves; Scott Grundy; Rhian Gwilliam; Ulf Gyllensten; Samy Hadjadj; Göran Hallmans; Naomi Hammond; Xijing Han; Anna -LiisaHartikainen; Neelam Hassanali; Caroline Hayward; Simon C. Heath; Serge Hercberg; Christian Herder; Andrew A. Hicks; David R. Hillman; Aroon D. Hingorani; Albert Hofman; Jennie Hui; Joe Hung; Bo Isomaa; Paul R.V. Johnson; Torben Jørgensen; Antti Jula; Marika Kaakinen; Jaakko Kaprio; Y. AnteroKesaniemi; Mika Kivimaki; Beatrice Knight; Seppo Koskinen; Peter Kovacs; Kirsten Ohm Kyvik; G. Mark Lathrop; Debbie A. Lawlor; Olivier Le Bacquer; Cécile Lecoeur; Yun Li; Valeriya Lyssenko; Robert Mahley; Massimo Mangino; Alisa K. Manning; María TeresaMartínez-Larrad; Jarred B. McAteer; Laura J. McCulloch; Ruth McPherson; Christa Meisinger; David Melzer; David Meyre; Braxton D. Mitchell; Mario A. Morken; Sutapa Mukherjee; Silvia Naitza; Narisu Narisu; Matthew J. Neville; Ben A. Oostra; Marco Orrù; Ruth Pakyz; Colin N. APalmer; Giuseppe Paolisso; Cristian Pattaro; Daniel Pearson; John F. Peden; Nancy L. Pedersen; Markus Perola; Andreas F.H. Pfeiffer; Irene Pichler; Ozren Polasek; Danielle Posthuma; Simon C. Potter; Anneli Pouta; Michael A. Province; Bruce M. Psaty; Wolfgang Rathmann; Nigel W. Rayner; Kenneth Rice; Samuli Ripatti; Fernando Rivadeneira; Michael Roden; Olov Rolandsson; Annelli Sandbaek; Manjinder Sandhu; Serena Sanna; Avan Aihie Sayer; Paul Scheet; Laura J. Scott; Udo Seedorf; Stephen J. Sharp; Beverley Shields; Gunnar Sigursson; Eric J.G. Sijbrands; Angela Silveira; Laila Simpson; Andrew Singleton; Nicholas L. Smith; Ulla Sovio; Amy Swift; Holly Syddall; Ann -ChristineSyvänen; Toshiko Tanaka; Barbara Thorand; Jean Tichet; Anke Tönjes; Tiinamaija Tuomi; André G. Uitterlinden; Ko Willems Van Dijk; Mandy Van Hoek; Dhiraj Varma; Sophie Visvikis-Siest; Veronique Vitart; Nicole Vogelzangs; Gérard Waeber; Peter J. Wagner; Andrew Walley; G. BragiWalters; Kim L. Ward; Hugh Watkins; Michael N. Weedon; Sarah H. Wild; Gonneke Willemsen; Jaqueline C. MWitteman; John W. GYarnell; Eleftheria Zeggini; Diana Zelenika; Björn Zethelius; Guangju Zhai; Jing Hua Zhao; M. Carola Zillikens; Ingrid B. Borecki; Ruth J.F. Loos; Pierre Meneton; Patrik K.E. Magnusson; David M. Nathan; Gordon H. Williams; Andrew T. Hattersley; Kaisa Silander; Veikko Salomaa; George Davey Smith; Stefan R. Bornstein; Peter Schwarz; Joachim Spranger; Fredrik Karpe; Alan R. Shuldiner; Cyrus Cooper; George V. Dedoussis; Manuel Serrano-Ríos; Andrew D. Morris; Lars Lind; Lyle J. Palmer; Frank B. Hu; Paul W. Franks; Shah Ebrahim; Michael Marmot; W. H. Linda Kao; James S. Pankow; Michael J. Sampson; Johanna Kuusisto; Markku Laakso; Torben Hansen; Oluf Pedersen; Peter Paul Pramstaller; H. Erich Wichmann; Thomas Illig; Igor Rudan; Alan F. Wright; Michael Stumvoll; Harry Campbell; James F. Wilson

doi:10.1038/ng.520

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Josée Dupuis, Claudia Langenberg, Inga Prokopenko, Richa Saxena, Nicole Soranzo, Anne U. Jackson, Eleanor Wheeler, Nicole L. Glazer, Nabila Bouatia-Naji, Ulf Gyllensten, Cecilia M. Lindgren, Reedik Mägi, Andrew P. Morris, Joshua Randall, Toby Johnson, Paul Elliott, Denis Rybin, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Peter HennemanHarald Grallert, Abbas Dehghan, Jouke JanHottenga, Christopher S. Franklin, Pau Navarro, Kijoung Song, Anuj Goel, John R.B. Perry, Josephine M. Egan, Taina Lajunen, Niels Grarup, Thomas Sparsø, Alex Doney, Benjamin F. Voight, Heather M. Stringham, Man Li, Stavroula Kanoni, Peter Shrader, Christine Cavalcanti-Proença, Meena Kumari, Rafn Benediktsson, Nicholas J. Timpson, Christian Gieger, Carina Zabena, Ghislain Rocheleau, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'An Luan, Amanda Elliott, Steven A. McCarroll, Felicity Payne, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Kristin Ardlie, Yavuz Ariyurek, Beverley Balkau, Philip Barter, John P. Beilby, Yoav Ben-Shlomo, Rafn Benediktsson, Amanda J. Bennett, Sven Bergmann, Murielle Bochud, Eric Boerwinkle, Amélie Bonnefond, Lori L. Bonnycastle, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J. Bumpstead, Guillaume Charpentier, Yii Der IdaChen, Peter Chines, Robert Clarke, Lachlan J. McOin, Matthew N. Cooper, Marilyn Cornelis, Gabe Crawford, Laura Crisponi, Ian N.M. Day, Eco J.C. De Geus, Jerome Delplanque, Christian Dina, Michael R. Erdos, Annette C. Fedson, Antje Fischer-Rosinsky, Nita G. Forouhi, Caroline S. Fox, Rune Frants, Maria GraziaFranzosi, Pilar Galan, Mark O. Goodarzi, Jürgen Graessler, Christopher J. Groves, Scott Grundy, Rhian Gwilliam, Ulf Gyllensten, Samy Hadjadj, Göran Hallmans, Naomi Hammond, Xijing Han, Anna -LiisaHartikainen, Neelam Hassanali, Caroline Hayward, Simon C. Heath, Serge Hercberg, Christian Herder, Andrew A. Hicks, David R. Hillman, Aroon D. Hingorani, Albert Hofman, Jennie Hui, Joe Hung, Bo Isomaa, Paul R.V. Johnson, Torben Jørgensen, Antti Jula, Marika Kaakinen, Jaakko Kaprio, Y. AnteroKesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G. Mark Lathrop, Debbie A. Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Valeriya Lyssenko, Robert Mahley, Massimo Mangino, Alisa K. Manning, María TeresaMartínez-Larrad, Jarred B. McAteer, Laura J. McCulloch, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D. Mitchell, Mario A. Morken, Sutapa Mukherjee, Silvia Naitza, Narisu Narisu, Matthew J. Neville, Ben A. Oostra, Marco Orrù, Ruth Pakyz, Colin N. APalmer, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F. Peden, Nancy L. Pedersen, Markus Perola, Andreas F.H. Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C. Potter, Anneli Pouta, Michael A. Province, Bruce M. Psaty, Wolfgang Rathmann, Nigel W. Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Michael Roden, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Laura J. Scott, Udo Seedorf, Stephen J. Sharp, Beverley Shields, Gunnar Sigursson, Eric J.G. Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L. Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann -ChristineSyvänen, Toshiko Tanaka, Barbara Thorand, Jean Tichet, Anke Tönjes, Tiinamaija Tuomi, André G. Uitterlinden, Ko Willems Van Dijk, Mandy Van Hoek, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J. Wagner, Andrew Walley, G. BragiWalters, Kim L. Ward, Hugh Watkins, Michael N. Weedon, Sarah H. Wild, Gonneke Willemsen, Jaqueline C. MWitteman, John W. GYarnell, Eleftheria Zeggini, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M. Carola Zillikens, Ingrid B. Borecki, Ruth J.F. Loos, Pierre Meneton, Patrik K.E. Magnusson, David M. Nathan, Gordon H. Williams, Andrew T. Hattersley, Kaisa Silander, Veikko Salomaa, George Davey Smith, Stefan R. Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R. Shuldiner, Cyrus Cooper, George V. Dedoussis, Manuel Serrano-Ríos, Andrew D. Morris, Lars Lind, Lyle J. Palmer, Frank B. Hu, Paul W. Franks, Shah Ebrahim, Michael Marmot, W. H. Linda Kao, James S. Pankow, Michael J. Sampson, Johanna Kuusisto, Markku Laakso, Torben Hansen, Oluf Pedersen, Peter Paul Pramstaller, H. Erich Wichmann, Thomas Illig, Igor Rudan, Alan F. Wright, Michael Stumvoll, Harry Campbell, James F. Wilson

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

1787 Citations (Scopus)

Abstract

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Original language	English
Pages (from-to)	105-116
Number of pages	12
Journal	Nature Genetics
Volume	42
Issue number	2
Early online date	17 Jan 2010
DOIs	https://doi.org/10.1038/ng.520 https://doi.org/10.1038/ng0510-464a
Publication status	Published - Feb 2010
Externally published	Yes

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10.1038/ng.520Licence: In Copyright
10.1038/ng0510-464a

Cite this

Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A. U., Wheeler, E., Glazer, N. L., Bouatia-Naji, N., Gyllensten, U., Lindgren, C. M., Mägi, R., Morris, A. P., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., ... Wilson, J. F. (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics, 42(2), 105-116. https://doi.org/10.1038/ng.520, https://doi.org/10.1038/ng0510-464a

@article{514825e1d9734785958fa9a782801acf,

title = "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk",

abstract = "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.",

author = "Jos{\'e}e Dupuis and Claudia Langenberg and Inga Prokopenko and Richa Saxena and Nicole Soranzo and Jackson, {Anne U.} and Eleanor Wheeler and Glazer, {Nicole L.} and Nabila Bouatia-Naji and Ulf Gyllensten and Lindgren, {Cecilia M.} and Reedik M{\"a}gi and Morris, {Andrew P.} and Joshua Randall and Toby Johnson and Paul Elliott and Denis Rybin and Gudmar Thorleifsson and Valgerdur Steinthorsdottir and Peter Henneman and Harald Grallert and Abbas Dehghan and Jouke JanHottenga and Franklin, {Christopher S.} and Pau Navarro and Kijoung Song and Anuj Goel and Perry, {John R.B.} and Egan, {Josephine M.} and Taina Lajunen and Niels Grarup and Thomas Spars{\o} and Alex Doney and Voight, {Benjamin F.} and Stringham, {Heather M.} and Man Li and Stavroula Kanoni and Peter Shrader and Christine Cavalcanti-Proen{\c c}a and Meena Kumari and Rafn Benediktsson and Timpson, {Nicholas J.} and Christian Gieger and Carina Zabena and Ghislain Rocheleau and Erik Ingelsson and Ping An and Jeffrey O'Connell and Jian'An Luan and Amanda Elliott and McCarroll, {Steven A.} and Felicity Payne and Roccasecca, {Rosa Maria} and Fran{\c c}ois Pattou and Praveen Sethupathy and Kristin Ardlie and Yavuz Ariyurek and Beverley Balkau and Philip Barter and Beilby, {John P.} and Yoav Ben-Shlomo and Rafn Benediktsson and Bennett, {Amanda J.} and Sven Bergmann and Murielle Bochud and Eric Boerwinkle and Am{\'e}lie Bonnefond and Bonnycastle, {Lori L.} and Knut Borch-Johnsen and Yvonne B{\"o}ttcher and Eric Brunner and Bumpstead, {Suzannah J.} and Guillaume Charpentier and {Der IdaChen}, Yii and Peter Chines and Robert Clarke and McOin, {Lachlan J.} and Cooper, {Matthew N.} and Marilyn Cornelis and Gabe Crawford and Laura Crisponi and Day, {Ian N.M.} and {De Geus}, {Eco J.C.} and Jerome Delplanque and Christian Dina and Erdos, {Michael R.} and Fedson, {Annette C.} and Antje Fischer-Rosinsky and Forouhi, {Nita G.} and Fox, {Caroline S.} and Rune Frants and Maria GraziaFranzosi and Pilar Galan and Goodarzi, {Mark O.} and J{\"u}rgen Graessler and Groves, {Christopher J.} and Scott Grundy and Rhian Gwilliam and Ulf Gyllensten and Samy Hadjadj and G{\"o}ran Hallmans and Naomi Hammond and Xijing Han and Anna -LiisaHartikainen and Neelam Hassanali and Caroline Hayward and Heath, {Simon C.} and Serge Hercberg and Christian Herder and Hicks, {Andrew A.} and Hillman, {David R.} and Hingorani, {Aroon D.} and Albert Hofman and Jennie Hui and Joe Hung and Bo Isomaa and Johnson, {Paul R.V.} and Torben J{\o}rgensen and Antti Jula and Marika Kaakinen and Jaakko Kaprio and Y. AnteroKesaniemi and Mika Kivimaki and Beatrice Knight and Seppo Koskinen and Peter Kovacs and Kyvik, {Kirsten Ohm} and Lathrop, {G. Mark} and Lawlor, {Debbie A.} and Bacquer, {Olivier Le} and C{\'e}cile Lecoeur and Yun Li and Valeriya Lyssenko and Robert Mahley and Massimo Mangino and Manning, {Alisa K.} and Mar{\'i}a TeresaMart{\'i}nez-Larrad and McAteer, {Jarred B.} and McCulloch, {Laura J.} and Ruth McPherson and Christa Meisinger and David Melzer and David Meyre and Mitchell, {Braxton D.} and Morken, {Mario A.} and Sutapa Mukherjee and Silvia Naitza and Narisu Narisu and Neville, {Matthew J.} and Oostra, {Ben A.} and Marco Orr{\`u} and Ruth Pakyz and APalmer, {Colin N.} and Giuseppe Paolisso and Cristian Pattaro and Daniel Pearson and Peden, {John F.} and Pedersen, {Nancy L.} and Markus Perola and Pfeiffer, {Andreas F.H.} and Irene Pichler and Ozren Polasek and Danielle Posthuma and Potter, {Simon C.} and Anneli Pouta and Province, {Michael A.} and Psaty, {Bruce M.} and Wolfgang Rathmann and Rayner, {Nigel W.} and Kenneth Rice and Samuli Ripatti and Fernando Rivadeneira and Michael Roden and Olov Rolandsson and Annelli Sandbaek and Manjinder Sandhu and Serena Sanna and Sayer, {Avan Aihie} and Paul Scheet and Scott, {Laura J.} and Udo Seedorf and Sharp, {Stephen J.} and Beverley Shields and Gunnar Sigursson and Sijbrands, {Eric J.G.} and Angela Silveira and Laila Simpson and Andrew Singleton and Smith, {Nicholas L.} and Ulla Sovio and Amy Swift and Holly Syddall and Ann -ChristineSyv{\"a}nen and Toshiko Tanaka and Barbara Thorand and Jean Tichet and Anke T{\"o}njes and Tiinamaija Tuomi and Uitterlinden, {Andr{\'e} G.} and {Van Dijk}, {Ko Willems} and Hoek, {Mandy Van} and Dhiraj Varma and Sophie Visvikis-Siest and Veronique Vitart and Nicole Vogelzangs and G{\'e}rard Waeber and Wagner, {Peter J.} and Andrew Walley and G. BragiWalters and Ward, {Kim L.} and Hugh Watkins and Weedon, {Michael N.} and Wild, {Sarah H.} and Gonneke Willemsen and MWitteman, {Jaqueline C.} and GYarnell, {John W.} and Eleftheria Zeggini and Diana Zelenika and Bj{\"o}rn Zethelius and Guangju Zhai and Zhao, {Jing Hua} and Zillikens, {M. Carola} and Borecki, {Ingrid B.} and Loos, {Ruth J.F.} and Pierre Meneton and Magnusson, {Patrik K.E.} and Nathan, {David M.} and Williams, {Gordon H.} and Hattersley, {Andrew T.} and Kaisa Silander and Veikko Salomaa and Smith, {George Davey} and Bornstein, {Stefan R.} and Peter Schwarz and Joachim Spranger and Fredrik Karpe and Shuldiner, {Alan R.} and Cyrus Cooper and Dedoussis, {George V.} and Manuel Serrano-R{\'i}os and Morris, {Andrew D.} and Lars Lind and Palmer, {Lyle J.} and Hu, {Frank B.} and Franks, {Paul W.} and Shah Ebrahim and Michael Marmot and {Linda Kao}, {W. H.} and Pankow, {James S.} and Sampson, {Michael J.} and Johanna Kuusisto and Markku Laakso and Torben Hansen and Oluf Pedersen and Pramstaller, {Peter Paul} and Wichmann, {H. Erich} and Thomas Illig and Igor Rudan and Wright, {Alan F.} and Michael Stumvoll and Harry Campbell and Wilson, {James F.}",

year = "2010",

month = feb,

doi = "10.1038/ng.520",

language = "English",

volume = "42",

pages = "105--116",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gyllensten, U, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, JanHottenga, J, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Benediktsson, R, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, JA, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Der IdaChen, Y, Chines, P, Clarke, R, McOin, LJ, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, De Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, GraziaFranzosi, M, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, -LiisaHartikainen, A, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jørgensen, T, Jula, A, Kaakinen, M, Kaprio, J, AnteroKesaniemi, Y, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Bacquer, OL, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, TeresaMartínez-Larrad, M, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orrù, M, Pakyz, R, APalmer, CN, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigursson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, -ChristineSyvänen, A, Tanaka, T, Thorand, B, Tichet, J, Tönjes, A, Tuomi, T, Uitterlinden, AG, Van Dijk, KW, Hoek, MV, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, BragiWalters, G, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, MWitteman, JC, GYarnell, JW, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Ríos, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Linda Kao, WH, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H & Wilson, JF 2010, 'New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk', Nature Genetics, vol. 42, no. 2, pp. 105-116. https://doi.org/10.1038/ng.520, https://doi.org/10.1038/ng0510-464a

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. / Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga et al.
In: Nature Genetics, Vol. 42, No. 2, 02.2010, p. 105-116.

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

TY - JOUR

T1 - New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

T2 - New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

AU - Dupuis, Josée

AU - Langenberg, Claudia

AU - Prokopenko, Inga

AU - Saxena, Richa

AU - Soranzo, Nicole

AU - Jackson, Anne U.

AU - Wheeler, Eleanor

AU - Glazer, Nicole L.

AU - Bouatia-Naji, Nabila

AU - Gyllensten, Ulf

AU - Lindgren, Cecilia M.

AU - Mägi, Reedik

AU - Morris, Andrew P.

AU - Randall, Joshua

AU - Johnson, Toby

AU - Elliott, Paul

AU - Rybin, Denis

AU - Thorleifsson, Gudmar

AU - Steinthorsdottir, Valgerdur

AU - Henneman, Peter

AU - Grallert, Harald

AU - Dehghan, Abbas

AU - JanHottenga, Jouke

AU - Franklin, Christopher S.

AU - Navarro, Pau

AU - Song, Kijoung

AU - Goel, Anuj

AU - Perry, John R.B.

AU - Egan, Josephine M.

AU - Lajunen, Taina

AU - Grarup, Niels

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AU - Wilson, James F.

PY - 2010/2

Y1 - 2010/2

N2 - Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

AB - Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

UR - http://www.scopus.com/inward/record.url?scp=75749086085&partnerID=8YFLogxK

U2 - 10.1038/ng.520

DO - 10.1038/ng.520

M3 - Article

AN - SCOPUS:75749086085

SN - 1061-4036

VL - 42

SP - 105

EP - 116

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics. 2010 Feb;42(2):105-116. Epub 2010 Jan 17. doi: 10.1038/ng.520, 10.1038/ng0510-464a

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

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