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, Anna L. Gloyn, Cecilia M. Lindgren, Reedik Mägi, Andrew P. Morris, Joshua Randall, Toby Johnson, Paul Elliott, Denis Rybin, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Peter Henneman & 283 others 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, Lu Qi, 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 M 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, Richard N. Bergman, Thomas A. Buchanan, Francis S. Collins, Karen L. Mohlke, Jaakko Tuomilehto, Timo T. Valle, David Altshuler, Jerome I. Rotter, David S. Siscovick, Brenda W J H Penninx, Dorret I. Boomsma, Panos Deloukas, Timothy D. Spector, Timothy M. Frayling, Luigi Ferrucci, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson, Cornelia M. Van Duijn, Yurii S. Aulchenko, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo -RiittaJarvelin, Dawn M. Waterworth, Peter Vollenweider, Leena Peltonen, Vincent Mooser, Goncalo R. Abecasis, Nicholas J. Wareham, Robert Sladek, Philippe Froguel, Richard M. Watanabe, James B. Meigs, Leif Groop, Michael Boehnke, Mark I. McCarthy, Jose C. Florez, Inês Barroso

Research output: Contribution to journalArticle

1311 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 languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalNature Genetics
Volume42
Issue number2
DOIs
StatePublished - Feb 2010

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Genetic Loci
Type 2 Diabetes Mellitus
Fasting
Homeostasis
Glucose
Insulin Resistance
Insulin
Genome-Wide Association Study
Genes
Meta-Analysis
Signal Transduction
Cell Proliferation
B-insulin

ASJC Scopus subject areas

  • Genetics

Cite this

Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A. U., ... Barroso, I. (2010). 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

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. / Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U.; Wheeler, Eleanor; Glazer, Nicole L.; Bouatia-Naji, Nabila; Gloyn, Anna L.; Lindgren, Cecilia M.; Mägi, Reedik; Morris, Andrew P.; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; JanHottenga, Jouke; Franklin, Christopher S.; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M.; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F.; Stringham, Heather M.; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J.; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'An; Elliott, Amanda; McCarroll, Steven A.; Payne, Felicity; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ardlie, Kristin; Ariyurek, Yavuz; Balkau, Beverley; Barter, Philip; Beilby, John P.; Ben-Shlomo, Yoav; Benediktsson, Rafn; Bennett, Amanda J.; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bonnefond, Amélie; Bonnycastle, Lori L.; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J.; Charpentier, Guillaume; Der IdaChen, Yii; Chines, Peter; Clarke, Robert; McOin, Lachlan J.; Cooper, Matthew N.; Cornelis, Marilyn; Crawford, Gabe; Crisponi, Laura; Day, Ian N M; De Geus, Eco J C; Delplanque, Jerome; Dina, Christian; Erdos, Michael R.; Fedson, Annette C.; Fischer-Rosinsky, Antje; Forouhi, Nita G.; Fox, Caroline S.; Frants, Rune; GraziaFranzosi, Maria; Galan, Pilar; Goodarzi, Mark O.; Graessler, Jürgen; Groves, Christopher J.; Grundy, Scott M; Gwilliam, Rhian; Gyllensten, Ulf; Hadjadj, Samy; Hallmans, Göran; Hammond, Naomi; Han, Xijing; -LiisaHartikainen, Anna; Hassanali, Neelam; Hayward, Caroline; Heath, Simon C.; Hercberg, Serge; Herder, Christian; Hicks, Andrew A.; Hillman, David R.; Hingorani, Aroon D.; Hofman, Albert; Hui, Jennie; Hung, Joe; Isomaa, Bo; Johnson, Paul R V; Jørgensen, Torben; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; AnteroKesaniemi, Y.; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G. Mark; Lawlor, Debbie A.; Bacquer, Olivier Le; Lecoeur, Cécile; Li, Yun; Lyssenko, Valeriya; Mahley, Robert; Mangino, Massimo; Manning, Alisa K.; TeresaMartínez-Larrad, María; McAteer, Jarred B.; McCulloch, Laura J.; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D.; Morken, Mario A.; Mukherjee, Sutapa; Naitza, Silvia; Narisu, Narisu; Neville, Matthew J.; Oostra, Ben A.; Orrù, Marco; Pakyz, Ruth; APalmer, Colin N.; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F.; Pedersen, Nancy L.; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C.; Pouta, Anneli; Province, Michael A.; Psaty, Bruce M.; Rathmann, Wolfgang; Rayner, Nigel W.; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Roden, Michael; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Scott, Laura J.; Seedorf, Udo; Sharp, Stephen J.; Shields, Beverley; Sigursson, Gunnar; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L.; Sovio, Ulla; Swift, Amy; Syddall, Holly; -ChristineSyvänen, Ann; Tanaka, Toshiko; Thorand, Barbara; Tichet, Jean; Tönjes, Anke; Tuomi, Tiinamaija; Uitterlinden, André G.; Van Dijk, Ko Willems; Hoek, Mandy Van; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J.; Walley, Andrew; BragiWalters, G.; Ward, Kim L.; Watkins, Hugh; Weedon, Michael N.; Wild, Sarah H.; Willemsen, Gonneke; MWitteman, Jaqueline C.; GYarnell, John W.; Zeggini, Eleftheria; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M. Carola; Borecki, Ingrid B.; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M.; Williams, Gordon H.; Hattersley, Andrew T.; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R.; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R.; Cooper, Cyrus; Dedoussis, George V.; Serrano-Ríos, Manuel; Morris, Andrew D.; Lind, Lars; Palmer, Lyle J.; Hu, Frank B.; Franks, Paul W.; Ebrahim, Shah; Marmot, Michael; Linda Kao, W. H.; Pankow, James S.; Sampson, Michael J.; Kuusisto, Johanna; Laakso, Markku; Hansen, Torben; Pedersen, Oluf; Pramstaller, Peter Paul; Wichmann, H. Erich; Illig, Thomas; Rudan, Igor; Wright, Alan F.; Stumvoll, Michael; Campbell, Harry; Wilson, James F.; Bergman, Richard N.; Buchanan, Thomas A.; Collins, Francis S.; Mohlke, Karen L.; Tuomilehto, Jaakko; Valle, Timo T.; Altshuler, David; Rotter, Jerome I.; Siscovick, David S.; Penninx, Brenda W J H; Boomsma, Dorret I.; Deloukas, Panos; Spector, Timothy D.; Frayling, Timothy M.; Ferrucci, Luigi; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; Van Duijn, Cornelia M.; Aulchenko, Yurii S.; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; -RiittaJarvelin, Marjo; Waterworth, Dawn M.; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Abecasis, Goncalo R.; Wareham, Nicholas J.; Sladek, Robert; Froguel, Philippe; Watanabe, Richard M.; Meigs, James B.; Groop, Leif; Boehnke, Michael; McCarthy, Mark I.; Florez, Jose C.; Barroso, Inês.

In: Nature Genetics, Vol. 42, No. 2, 02.2010, p. 105-116.

Research output: Contribution to journalArticle

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, 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, Qi, L, 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, SM, 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, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, -RiittaJarvelin, M, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC & Barroso, I 2010, '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
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. Nature Genetics. 2010 Feb;42(2):105-116. https://doi.org/10.1038/ng.520
Dupuis, Josée ; Langenberg, Claudia ; Prokopenko, Inga ; Saxena, Richa ; Soranzo, Nicole ; Jackson, Anne U. ; Wheeler, Eleanor ; Glazer, Nicole L. ; Bouatia-Naji, Nabila ; Gloyn, Anna L. ; Lindgren, Cecilia M. ; Mägi, Reedik ; Morris, Andrew P. ; Randall, Joshua ; Johnson, Toby ; Elliott, Paul ; Rybin, Denis ; Thorleifsson, Gudmar ; Steinthorsdottir, Valgerdur ; Henneman, Peter ; Grallert, Harald ; Dehghan, Abbas ; JanHottenga, Jouke ; Franklin, Christopher S. ; Navarro, Pau ; Song, Kijoung ; Goel, Anuj ; Perry, John R B ; Egan, Josephine M. ; Lajunen, Taina ; Grarup, Niels ; Sparsø, Thomas ; Doney, Alex ; Voight, Benjamin F. ; Stringham, Heather M. ; Li, Man ; Kanoni, Stavroula ; Shrader, Peter ; Cavalcanti-Proença, Christine ; Kumari, Meena ; Qi, Lu ; Timpson, Nicholas J. ; Gieger, Christian ; Zabena, Carina ; Rocheleau, Ghislain ; Ingelsson, Erik ; An, Ping ; O'Connell, Jeffrey ; Luan, Jian'An ; Elliott, Amanda ; McCarroll, Steven A. ; Payne, Felicity ; Roccasecca, Rosa Maria ; Pattou, François ; Sethupathy, Praveen ; Ardlie, Kristin ; Ariyurek, Yavuz ; Balkau, Beverley ; Barter, Philip ; Beilby, John P. ; Ben-Shlomo, Yoav ; Benediktsson, Rafn ; Bennett, Amanda J. ; Bergmann, Sven ; Bochud, Murielle ; Boerwinkle, Eric ; Bonnefond, Amélie ; Bonnycastle, Lori L. ; Borch-Johnsen, Knut ; Böttcher, Yvonne ; Brunner, Eric ; Bumpstead, Suzannah J. ; Charpentier, Guillaume ; Der IdaChen, Yii ; Chines, Peter ; Clarke, Robert ; McOin, Lachlan J. ; Cooper, Matthew N. ; Cornelis, Marilyn ; Crawford, Gabe ; Crisponi, Laura ; Day, Ian N M ; De Geus, Eco J C ; Delplanque, Jerome ; Dina, Christian ; Erdos, Michael R. ; Fedson, Annette C. ; Fischer-Rosinsky, Antje ; Forouhi, Nita G. ; Fox, Caroline S. ; Frants, Rune ; GraziaFranzosi, Maria ; Galan, Pilar ; Goodarzi, Mark O. ; Graessler, Jürgen ; Groves, Christopher J. ; Grundy, Scott M ; Gwilliam, Rhian ; Gyllensten, Ulf ; Hadjadj, Samy ; Hallmans, Göran ; Hammond, Naomi ; Han, Xijing ; -LiisaHartikainen, Anna ; Hassanali, Neelam ; Hayward, Caroline ; Heath, Simon C. ; Hercberg, Serge ; Herder, Christian ; Hicks, Andrew A. ; Hillman, David R. ; Hingorani, Aroon D. ; Hofman, Albert ; Hui, Jennie ; Hung, Joe ; Isomaa, Bo ; Johnson, Paul R V ; Jørgensen, Torben ; Jula, Antti ; Kaakinen, Marika ; Kaprio, Jaakko ; AnteroKesaniemi, Y. ; Kivimaki, Mika ; Knight, Beatrice ; Koskinen, Seppo ; Kovacs, Peter ; Kyvik, Kirsten Ohm ; Lathrop, G. Mark ; Lawlor, Debbie A. ; Bacquer, Olivier Le ; Lecoeur, Cécile ; Li, Yun ; Lyssenko, Valeriya ; Mahley, Robert ; Mangino, Massimo ; Manning, Alisa K. ; TeresaMartínez-Larrad, María ; McAteer, Jarred B. ; McCulloch, Laura J. ; McPherson, Ruth ; Meisinger, Christa ; Melzer, David ; Meyre, David ; Mitchell, Braxton D. ; Morken, Mario A. ; Mukherjee, Sutapa ; Naitza, Silvia ; Narisu, Narisu ; Neville, Matthew J. ; Oostra, Ben A. ; Orrù, Marco ; Pakyz, Ruth ; APalmer, Colin N. ; Paolisso, Giuseppe ; Pattaro, Cristian ; Pearson, Daniel ; Peden, John F. ; Pedersen, Nancy L. ; Perola, Markus ; Pfeiffer, Andreas F H ; Pichler, Irene ; Polasek, Ozren ; Posthuma, Danielle ; Potter, Simon C. ; Pouta, Anneli ; Province, Michael A. ; Psaty, Bruce M. ; Rathmann, Wolfgang ; Rayner, Nigel W. ; Rice, Kenneth ; Ripatti, Samuli ; Rivadeneira, Fernando ; Roden, Michael ; Rolandsson, Olov ; Sandbaek, Annelli ; Sandhu, Manjinder ; Sanna, Serena ; Sayer, Avan Aihie ; Scheet, Paul ; Scott, Laura J. ; Seedorf, Udo ; Sharp, Stephen J. ; Shields, Beverley ; Sigursson, Gunnar ; Sijbrands, Eric J G ; Silveira, Angela ; Simpson, Laila ; Singleton, Andrew ; Smith, Nicholas L. ; Sovio, Ulla ; Swift, Amy ; Syddall, Holly ; -ChristineSyvänen, Ann ; Tanaka, Toshiko ; Thorand, Barbara ; Tichet, Jean ; Tönjes, Anke ; Tuomi, Tiinamaija ; Uitterlinden, André G. ; Van Dijk, Ko Willems ; Hoek, Mandy Van ; Varma, Dhiraj ; Visvikis-Siest, Sophie ; Vitart, Veronique ; Vogelzangs, Nicole ; Waeber, Gérard ; Wagner, Peter J. ; Walley, Andrew ; BragiWalters, G. ; Ward, Kim L. ; Watkins, Hugh ; Weedon, Michael N. ; Wild, Sarah H. ; Willemsen, Gonneke ; MWitteman, Jaqueline C. ; GYarnell, John W. ; Zeggini, Eleftheria ; Zelenika, Diana ; Zethelius, Björn ; Zhai, Guangju ; Zhao, Jing Hua ; Zillikens, M. Carola ; Borecki, Ingrid B. ; Loos, Ruth J F ; Meneton, Pierre ; Magnusson, Patrik K E ; Nathan, David M. ; Williams, Gordon H. ; Hattersley, Andrew T. ; Silander, Kaisa ; Salomaa, Veikko ; Smith, George Davey ; Bornstein, Stefan R. ; Schwarz, Peter ; Spranger, Joachim ; Karpe, Fredrik ; Shuldiner, Alan R. ; Cooper, Cyrus ; Dedoussis, George V. ; Serrano-Ríos, Manuel ; Morris, Andrew D. ; Lind, Lars ; Palmer, Lyle J. ; Hu, Frank B. ; Franks, Paul W. ; Ebrahim, Shah ; Marmot, Michael ; Linda Kao, W. H. ; Pankow, James S. ; Sampson, Michael J. ; Kuusisto, Johanna ; Laakso, Markku ; Hansen, Torben ; Pedersen, Oluf ; Pramstaller, Peter Paul ; Wichmann, H. Erich ; Illig, Thomas ; Rudan, Igor ; Wright, Alan F. ; Stumvoll, Michael ; Campbell, Harry ; Wilson, James F. ; Bergman, Richard N. ; Buchanan, Thomas A. ; Collins, Francis S. ; Mohlke, Karen L. ; Tuomilehto, Jaakko ; Valle, Timo T. ; Altshuler, David ; Rotter, Jerome I. ; Siscovick, David S. ; Penninx, Brenda W J H ; Boomsma, Dorret I. ; Deloukas, Panos ; Spector, Timothy D. ; Frayling, Timothy M. ; Ferrucci, Luigi ; Kong, Augustine ; Thorsteinsdottir, Unnur ; Stefansson, Kari ; Van Duijn, Cornelia M. ; Aulchenko, Yurii S. ; Cao, Antonio ; Scuteri, Angelo ; Schlessinger, David ; Uda, Manuela ; Ruokonen, Aimo ; -RiittaJarvelin, Marjo ; Waterworth, Dawn M. ; Vollenweider, Peter ; Peltonen, Leena ; Mooser, Vincent ; Abecasis, Goncalo R. ; Wareham, Nicholas J. ; Sladek, Robert ; Froguel, Philippe ; Watanabe, Richard M. ; Meigs, James B. ; Groop, Leif ; Boehnke, Michael ; McCarthy, Mark I. ; Florez, Jose C. ; Barroso, Inês. / New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. In: Nature Genetics. 2010 ; Vol. 42, No. 2. pp. 105-116.
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title = "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 Gloyn, {Anna L.} 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{\cc}a and Meena Kumari and Lu Qi 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{\cc}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 Grundy, {Scott M} 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.} and Bergman, {Richard N.} and Buchanan, {Thomas A.} and Collins, {Francis S.} and Mohlke, {Karen L.} and Jaakko Tuomilehto and Valle, {Timo T.} and David Altshuler and Rotter, {Jerome I.} and Siscovick, {David S.} and Penninx, {Brenda W J H} and Boomsma, {Dorret I.} and Panos Deloukas and Spector, {Timothy D.} and Frayling, {Timothy M.} and Luigi Ferrucci and Augustine Kong and Unnur Thorsteinsdottir and Kari Stefansson and {Van Duijn}, {Cornelia M.} and Aulchenko, {Yurii S.} and Antonio Cao and Angelo Scuteri and David Schlessinger and Manuela Uda and Aimo Ruokonen and Marjo -RiittaJarvelin and Waterworth, {Dawn M.} and Peter Vollenweider and Leena Peltonen and Vincent Mooser and Abecasis, {Goncalo R.} and Wareham, {Nicholas J.} and Robert Sladek and Philippe Froguel and Watanabe, {Richard M.} and Meigs, {James B.} and Leif Groop and Michael Boehnke and McCarthy, {Mark I.} and Florez, {Jose C.} and In{\^e}s Barroso",
year = "2010",
month = "2",
doi = "10.1038/ng.520",
language = "English (US)",
volume = "42",
pages = "105--116",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - 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 - Gloyn, Anna L.

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

AU - Sparsø, Thomas

AU - Doney, Alex

AU - Voight, Benjamin F.

AU - Stringham, Heather M.

AU - Li, Man

AU - Kanoni, Stavroula

AU - Shrader, Peter

AU - Cavalcanti-Proença, Christine

AU - Kumari, Meena

AU - Qi, Lu

AU - Timpson, Nicholas J.

AU - Gieger, Christian

AU - Zabena, Carina

AU - Rocheleau, Ghislain

AU - Ingelsson, Erik

AU - An, Ping

AU - O'Connell, Jeffrey

AU - Luan, Jian'An

AU - Elliott, Amanda

AU - McCarroll, Steven A.

AU - Payne, Felicity

AU - Roccasecca, Rosa Maria

AU - Pattou, François

AU - Sethupathy, Praveen

AU - Ardlie, Kristin

AU - Ariyurek, Yavuz

AU - Balkau, Beverley

AU - Barter, Philip

AU - Beilby, John P.

AU - Ben-Shlomo, Yoav

AU - Benediktsson, Rafn

AU - Bennett, Amanda J.

AU - Bergmann, Sven

AU - Bochud, Murielle

AU - Boerwinkle, Eric

AU - Bonnefond, Amélie

AU - Bonnycastle, Lori L.

AU - Borch-Johnsen, Knut

AU - Böttcher, Yvonne

AU - Brunner, Eric

AU - Bumpstead, Suzannah J.

AU - Charpentier, Guillaume

AU - Der IdaChen, Yii

AU - Chines, Peter

AU - Clarke, Robert

AU - McOin, Lachlan J.

AU - Cooper, Matthew N.

AU - Cornelis, Marilyn

AU - Crawford, Gabe

AU - Crisponi, Laura

AU - Day, Ian N M

AU - De Geus, Eco J C

AU - Delplanque, Jerome

AU - Dina, Christian

AU - Erdos, Michael R.

AU - Fedson, Annette C.

AU - Fischer-Rosinsky, Antje

AU - Forouhi, Nita G.

AU - Fox, Caroline S.

AU - Frants, Rune

AU - GraziaFranzosi, Maria

AU - Galan, Pilar

AU - Goodarzi, Mark O.

AU - Graessler, Jürgen

AU - Groves, Christopher J.

AU - Grundy, Scott M

AU - Gwilliam, Rhian

AU - Gyllensten, Ulf

AU - Hadjadj, Samy

AU - Hallmans, Göran

AU - Hammond, Naomi

AU - Han, Xijing

AU - -LiisaHartikainen, Anna

AU - Hassanali, Neelam

AU - Hayward, Caroline

AU - Heath, Simon C.

AU - Hercberg, Serge

AU - Herder, Christian

AU - Hicks, Andrew A.

AU - Hillman, David R.

AU - Hingorani, Aroon D.

AU - Hofman, Albert

AU - Hui, Jennie

AU - Hung, Joe

AU - Isomaa, Bo

AU - Johnson, Paul R V

AU - Jørgensen, Torben

AU - Jula, Antti

AU - Kaakinen, Marika

AU - Kaprio, Jaakko

AU - AnteroKesaniemi, Y.

AU - Kivimaki, Mika

AU - Knight, Beatrice

AU - Koskinen, Seppo

AU - Kovacs, Peter

AU - Kyvik, Kirsten Ohm

AU - Lathrop, G. Mark

AU - Lawlor, Debbie A.

AU - Bacquer, Olivier Le

AU - Lecoeur, Cécile

AU - Li, Yun

AU - Lyssenko, Valeriya

AU - Mahley, Robert

AU - Mangino, Massimo

AU - Manning, Alisa K.

AU - TeresaMartínez-Larrad, María

AU - McAteer, Jarred B.

AU - McCulloch, Laura J.

AU - McPherson, Ruth

AU - Meisinger, Christa

AU - Melzer, David

AU - Meyre, David

AU - Mitchell, Braxton D.

AU - Morken, Mario A.

AU - Mukherjee, Sutapa

AU - Naitza, Silvia

AU - Narisu, Narisu

AU - Neville, Matthew J.

AU - Oostra, Ben A.

AU - Orrù, Marco

AU - Pakyz, Ruth

AU - APalmer, Colin N.

AU - Paolisso, Giuseppe

AU - Pattaro, Cristian

AU - Pearson, Daniel

AU - Peden, John F.

AU - Pedersen, Nancy L.

AU - Perola, Markus

AU - Pfeiffer, Andreas F H

AU - Pichler, Irene

AU - Polasek, Ozren

AU - Posthuma, Danielle

AU - Potter, Simon C.

AU - Pouta, Anneli

AU - Province, Michael A.

AU - Psaty, Bruce M.

AU - Rathmann, Wolfgang

AU - Rayner, Nigel W.

AU - Rice, Kenneth

AU - Ripatti, Samuli

AU - Rivadeneira, Fernando

AU - Roden, Michael

AU - Rolandsson, Olov

AU - Sandbaek, Annelli

AU - Sandhu, Manjinder

AU - Sanna, Serena

AU - Sayer, Avan Aihie

AU - Scheet, Paul

AU - Scott, Laura J.

AU - Seedorf, Udo

AU - Sharp, Stephen J.

AU - Shields, Beverley

AU - Sigursson, Gunnar

AU - Sijbrands, Eric J G

AU - Silveira, Angela

AU - Simpson, Laila

AU - Singleton, Andrew

AU - Smith, Nicholas L.

AU - Sovio, Ulla

AU - Swift, Amy

AU - Syddall, Holly

AU - -ChristineSyvänen, Ann

AU - Tanaka, Toshiko

AU - Thorand, Barbara

AU - Tichet, Jean

AU - Tönjes, Anke

AU - Tuomi, Tiinamaija

AU - Uitterlinden, André G.

AU - Van Dijk, Ko Willems

AU - Hoek, Mandy Van

AU - Varma, Dhiraj

AU - Visvikis-Siest, Sophie

AU - Vitart, Veronique

AU - Vogelzangs, Nicole

AU - Waeber, Gérard

AU - Wagner, Peter J.

AU - Walley, Andrew

AU - BragiWalters, G.

AU - Ward, Kim L.

AU - Watkins, Hugh

AU - Weedon, Michael N.

AU - Wild, Sarah H.

AU - Willemsen, Gonneke

AU - MWitteman, Jaqueline C.

AU - GYarnell, John W.

AU - Zeggini, Eleftheria

AU - Zelenika, Diana

AU - Zethelius, Björn

AU - Zhai, Guangju

AU - Zhao, Jing Hua

AU - Zillikens, M. Carola

AU - Borecki, Ingrid B.

AU - Loos, Ruth J F

AU - Meneton, Pierre

AU - Magnusson, Patrik K E

AU - Nathan, David M.

AU - Williams, Gordon H.

AU - Hattersley, Andrew T.

AU - Silander, Kaisa

AU - Salomaa, Veikko

AU - Smith, George Davey

AU - Bornstein, Stefan R.

AU - Schwarz, Peter

AU - Spranger, Joachim

AU - Karpe, Fredrik

AU - Shuldiner, Alan R.

AU - Cooper, Cyrus

AU - Dedoussis, George V.

AU - Serrano-Ríos, Manuel

AU - Morris, Andrew D.

AU - Lind, Lars

AU - Palmer, Lyle J.

AU - Hu, Frank B.

AU - Franks, Paul W.

AU - Ebrahim, Shah

AU - Marmot, Michael

AU - Linda Kao, W. H.

AU - Pankow, James S.

AU - Sampson, Michael J.

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Pramstaller, Peter Paul

AU - Wichmann, H. Erich

AU - Illig, Thomas

AU - Rudan, Igor

AU - Wright, Alan F.

AU - Stumvoll, Michael

AU - Campbell, Harry

AU - Wilson, James F.

AU - Bergman, Richard N.

AU - Buchanan, Thomas A.

AU - Collins, Francis S.

AU - Mohlke, Karen L.

AU - Tuomilehto, Jaakko

AU - Valle, Timo T.

AU - Altshuler, David

AU - Rotter, Jerome I.

AU - Siscovick, David S.

AU - Penninx, Brenda W J H

AU - Boomsma, Dorret I.

AU - Deloukas, Panos

AU - Spector, Timothy D.

AU - Frayling, Timothy M.

AU - Ferrucci, Luigi

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Van Duijn, Cornelia M.

AU - Aulchenko, Yurii S.

AU - Cao, Antonio

AU - Scuteri, Angelo

AU - Schlessinger, David

AU - Uda, Manuela

AU - Ruokonen, Aimo

AU - -RiittaJarvelin, Marjo

AU - Waterworth, Dawn M.

AU - Vollenweider, Peter

AU - Peltonen, Leena

AU - Mooser, Vincent

AU - Abecasis, Goncalo R.

AU - Wareham, Nicholas J.

AU - Sladek, Robert

AU - Froguel, Philippe

AU - Watanabe, Richard M.

AU - Meigs, James B.

AU - Groop, Leif

AU - Boehnke, Michael

AU - McCarthy, Mark I.

AU - Florez, Jose C.

AU - Barroso, Inês

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.

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U2 - 10.1038/ng.520

DO - 10.1038/ng.520

M3 - Article

VL - 42

SP - 105

EP - 116

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -