Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Ys, Aulchenko; Yd, Chen; Wichmann, He Erich; Wilson, James F.; Williams, Gordon H.; Hivert, Marie-France; Saxena, Richa; Linda Kao, W. H.; Pankow, James S.; Langenberg, Claudia; Mf, Hivert; Tanaka, Toshiko; Jackson, Anne U.; Anluan, J.; Kao, Wh H. Linda; O’Connell, Jeffrey; Glazer, Nicole L.; Vollenweider, Peter; Dj, Couper; Manning, Alisa K.; Oconnell, J.; Stringham, Heather M.; Koettgen, Anna; Lyssenko, Valeriya; Ch, Andreasen; Boesgaard, Trine W.; Bouatia-Naji, Nabila; Bacquer, Olivier Le; Lecoeur, Cecile; Shrader, Peter; Dupuis, Josee; Ingelsson, Erik; Mn, Weedon; Couper, David J.; van Hoek, Mandy; O'Connell, Jeffrey; Js, Pankow; Rice, Kenneth; Böttcher, Yvonne; Song, Kijoung; Hoek, M.; Andreasen, Camilla H.; Dina, Christian; Bf, Voight; Köttgen, Anna; Li, Man; Le Bacquer, Olivier; Rn, Bergman; Pattou, François; Boettcher, Yvonne; Taneera, Jalal; Steinthorsdottir, Valgerdur; Sj, Bielinski; Luan, Jian’an; Rybin, Denis; Ll, Bonnycastle; Ardlie, Kristin; Sampson, Michael; Ta, Buchanan; Qi, Lu; Weedon, Michael N.; Sj, Bumpstead; Prokopenko, Inga; Aulchenko, Yurii S.; Voight, Benjamin F.; Crawford, Gabriel J.; Grallert, Harald; Johnson, Toby; Balkau, Beverley; Ps, Chines; Bergman, Richard N.; Grarup, Niels; Bielinski, Suzette J.; Fs, Collins; Ak, Manning; Bonnefond, Amélie; Bonnycastle, Lori Ll; Borch-Johnsen, Knut; Jm, Egan; Böttcher, Yvonne; Jørgensen, Torben; Brunner, Eric; Buchanan, Thomas A.; Mr, Erdos; Bumpstead, Suzannah J.; Au, Jackson; Cavalcanti-Proença, Christine; Hm, Stringham; Ng, Forouhi; Charpentier, Guillaume; Chen, Yii-Der Ida; Levy-Marchal, Claire; Chines, Peter S.; Cs, Fox; Collins, Francis S.; Cornelis, Marilyn; Wh, Kao; J. Crawford, Gabriel; Delplanque, Jerome; Doney, Alex; Mo, Goodarzi; Apalmer, C. N.; Egan, Josephine M.; Erdos, Michael R.; Zeggini, Eleftheria; Firmann, Mathieu; Jùrgensen, T.; Zhao, Jing Hua; Forouhi, Nita G.; Jb, McAteer; Fox, Caroline S.; Goodarzi, Mark O.; Graessler, Jürgen; Bd, Mitchell; Hingorani, Aroon; Tw, Boesgaard; Isomaa, Bo; Kl, Mohlke; Jorgensen, Torben; Nl, Glazer; Kivimaki, Mika; Tönjes, Anke; Kovacs, Peter; Ma, Morken; Krohn, Knut; Kumari, Meena; Cn, Palmer; Lauritzen, Torsten; Lévy-Marchal, Claire; Toenjes, Anke; Mayor, Vladimir; Aa, Sayer; McAteer, Jarred B.; Lj, Scott; Meyre, David; Mitchell, Braxton D.; Van Duijn, Cornelia; Mohlke, Karen L.; Consortium, G.; Morken, Mario A.; Sj, Sharp; Illig, Thomas; Narisu, Narisu; Ds, Siscovick; Palmer, Colin N. A.; Pakyz, Ruth; Erich Wichmann, H.; Nl, Smith; Pascoe, Laura; Duijn, C.; Payne, Felicity; Hu, Frank B.; Pearson, Daniel; Morris, Andrew D.; Rathmann, Wolfgang; Frayling, Timothy M.; Sandbaek, Annelli; Aj, Swift; Hattersley, Andrew T.; Sayer, Avan Aihie; Sparsù, T.; Scott, Laura J.; Tt, Valle; Sharp, Stephen J.; Thorsteinsdottir, Unnur; Sijbrands, Eric; Stefansson, Kari; Nilsson, Peter; Singleton, Andrew; Syvanen, Ann-Christine; Shuldiner, Alan R.; Siscovick, David S.; Walker, Mark; Smith, Nicholas L.; Bornstein, Stefan R.; Dm, Waterworth; Sparsø, Thomas; Schwarz, Peter; Swift, Amy J.; Jh, Zhao; Nathan, David M.; Syddall, Holly; Giant, Consortium; Thorleifsson, Gudmar; Kuusisto, Johanna; Laakso, Markku; Tönjes, Anke; Magic, Investigators; Cooper, Cyrus; Tuomi, Tiinamaija; Marmot, Michael; Ferrucci, Luigi; Tuomilehto, Jaakko; He, Wichmann; Mooser, Vincent; Valle, Timo Tt; Stumvoll, Michael; Jf, Wilson; Loos, Ruth J. F.; Waeber, Gerard; Altshuler, David; Fb, Hu; Walley, Andrew; Psaty, Bruce M.; Rotter, Jerome I.; Boerwinkle, Eric; Waterworth, Dawn M.; Ad, Morris; Hansen, Torben; Pedersen, Oluf; Tm, Frayling; Florez, Jose C.; McCarthy, Mark I.; At, Hattersley; Boehnke, Michael; Barroso, Inês; Sladek, Robert; Ac, Syvänen; Froguel, Philippe; Meigs, James B.; Ar, Shuldiner; Groop, Leif; Wareham, Nicholas J.; Giant Consortium, Magic Investigators; Watanabe, Richard M.; Rm, Watanabe

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Inga Prokopenko
Ys et al., 2010

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@article{Ys2010,
  abstract = {Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).},
  author = {Ys, Aulchenko and Yd, Chen and Wichmann, He Erich and Wilson, James F. and Williams, Gordon H. and Hivert, Marie-France and Saxena, Richa and Linda Kao, W. H. and Pankow, James S. and Langenberg, Claudia and Mf, Hivert and Tanaka, Toshiko and Jackson, Anne U. and Anluan, J. and Kao, Wh H. Linda and O’Connell, Jeffrey and Glazer, Nicole L. and Vollenweider, Peter and Dj, Couper and Manning, Alisa K. and Oconnell, J. and Stringham, Heather M. and Koettgen, Anna and Lyssenko, Valeriya and Ch, Andreasen and Boesgaard, Trine W. and Bouatia-Naji, Nabila and Bacquer, Olivier Le and Lecoeur, Cecile and Shrader, Peter and Dupuis, Josee and Ingelsson, Erik and Mn, Weedon and Couper, David J. and van Hoek, Mandy and O'Connell, Jeffrey and Js, Pankow and Rice, Kenneth and Böttcher, Yvonne and Song, Kijoung and Hoek, M. and Andreasen, Camilla H. and Dina, Christian and Bf, Voight and Köttgen, Anna and Li, Man and Le Bacquer, Olivier and Rn, Bergman and Pattou, François and Boettcher, Yvonne and Taneera, Jalal and Steinthorsdottir, Valgerdur and Sj, Bielinski and Luan, Jian’an and Rybin, Denis and Ll, Bonnycastle and Ardlie, Kristin and Sampson, Michael and Ta, Buchanan and Qi, Lu and Weedon, Michael N. and Sj, Bumpstead and Prokopenko, Inga and Aulchenko, Yurii S. and Voight, Benjamin F. and Crawford, Gabriel J. and Grallert, Harald and Johnson, Toby and Balkau, Beverley and Ps, Chines and Bergman, Richard N. and Grarup, Niels and Bielinski, Suzette J. and Fs, Collins and Ak, Manning and Bonnefond, Amélie and Bonnycastle, Lori Ll and Borch-Johnsen, Knut and Jm, Egan and Böttcher, Yvonne and Jørgensen, Torben and Brunner, Eric and Buchanan, Thomas A. and Mr, Erdos and Bumpstead, Suzannah J. and Au, Jackson and Cavalcanti-Proença, Christine and Hm, Stringham and Ng, Forouhi and Charpentier, Guillaume and Chen, Yii-Der Ida and Levy-Marchal, Claire and Chines, Peter S. and Cs, Fox and Collins, Francis S. and Cornelis, Marilyn and Wh, Kao and J. Crawford, Gabriel and Delplanque, Jerome and Doney, Alex and Mo, Goodarzi and Apalmer, C. N. and Egan, Josephine M. and Erdos, Michael R. and Zeggini, Eleftheria and Firmann, Mathieu and Jùrgensen, T. and Zhao, Jing Hua and Forouhi, Nita G. and Jb, McAteer and Fox, Caroline S. and Goodarzi, Mark O. and Graessler, Jürgen and Bd, Mitchell and Hingorani, Aroon and Tw, Boesgaard and Isomaa, Bo and Kl, Mohlke and Jorgensen, Torben and Nl, Glazer and Kivimaki, Mika and Tönjes, Anke and Kovacs, Peter and Ma, Morken and Krohn, Knut and Kumari, Meena and Cn, Palmer and Lauritzen, Torsten and Lévy-Marchal, Claire and Toenjes, Anke and Mayor, Vladimir and Aa, Sayer and McAteer, Jarred B. and Lj, Scott and Meyre, David and Mitchell, Braxton D. and Van Duijn, Cornelia and Mohlke, Karen L. and Consortium, G. and Morken, Mario A. and Sj, Sharp and Illig, Thomas and Narisu, Narisu and Ds, Siscovick and Palmer, Colin N. A. and Pakyz, Ruth and Erich Wichmann, H. and Nl, Smith and Pascoe, Laura and Duijn, C. and Payne, Felicity and Hu, Frank B. and Pearson, Daniel and Morris, Andrew D. and Rathmann, Wolfgang and Frayling, Timothy M. and Sandbaek, Annelli and Aj, Swift and Hattersley, Andrew T. and Sayer, Avan Aihie and Sparsù, T. and Scott, Laura J. and Tt, Valle and Sharp, Stephen J. and Thorsteinsdottir, Unnur and Sijbrands, Eric and Stefansson, Kari and Nilsson, Peter and Singleton, Andrew and Syvanen, Ann-Christine and Shuldiner, Alan R. and Siscovick, David S. and Walker, Mark and Smith, Nicholas L. and Bornstein, Stefan R. and Dm, Waterworth and Sparsø, Thomas and Schwarz, Peter and Swift, Amy J. and Jh, Zhao and Nathan, David M. and Syddall, Holly and Giant, Consortium and Thorleifsson, Gudmar and Kuusisto, Johanna and Laakso, Markku and Tönjes, Anke and Magic, Investigators and Cooper, Cyrus and Tuomi, Tiinamaija and Marmot, Michael and Ferrucci, Luigi and Tuomilehto, Jaakko and He, Wichmann and Mooser, Vincent and Valle, Timo Tt and Stumvoll, Michael and Jf, Wilson and Loos, Ruth J. F. and Waeber, Gerard and Altshuler, David and Fb, Hu and Walley, Andrew and Psaty, Bruce M. and Rotter, Jerome I. and Boerwinkle, Eric and Waterworth, Dawn M. and Ad, Morris and Hansen, Torben and Pedersen, Oluf and Tm, Frayling and Florez, Jose C. and McCarthy, Mark I. and At, Hattersley and Boehnke, Michael and Barroso, Inês and Sladek, Robert and Ac, Syvänen and Froguel, Philippe and Meigs, James B. and Ar, Shuldiner and Groop, Leif and Wareham, Nicholas J. and Giant Consortium, Magic Investigators and Watanabe, Richard M. and Rm, Watanabe},
  doi = {10.1038/ng.521},
  month = {jan},
  title = {Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge},
  url = {http://www.nature.com/articles/ng.521.pdf},
  year = {2010}
}

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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Journal article published in 2010 by Aulchenko Ys, Chen Yd, He Erich Wichmann, James F. Wilson, Gordon H. Williams, Marie-France Hivert, Richa Saxena, W. H. Linda Kao, James S. Pankow, Claudia Langenberg, Hivert Mf, Toshiko Tanaka, Anne U. Jackson, J. Anluan, Wh H. Linda Kao and other authors. Aulchenko Ys, Chen Yd, He Erich Wichmann, James F. Wilson, Gordon H. Williams, Marie-France Hivert, Richa Saxena, W. H. Linda Kao, James S. Pankow, Claudia Langenberg, Hivert Mf, Toshiko Tanaka, Anne U. Jackson, J. Anluan, Wh H. Linda Kao, Jeffrey O’Connell, Nicole L. Glazer, Peter Vollenweider, Couper Dj, Alisa K. Manning, J. Oconnell, Heather M. Stringham, Anna Koettgen, Valeriya Lyssenko, Andreasen Ch, Trine W. Boesgaard, Nabila Bouatia-Naji, Olivier Le Bacquer, Cecile Lecoeur, Peter Shrader, Josee Dupuis, Erik Ingelsson, Weedon Mn, David J. Couper, Mandy van Hoek, Jeffrey O'Connell, Pankow Js, Kenneth Rice, Yvonne Böttcher, Kijoung Song, M. Hoek, Camilla H. Andreasen, Christian Dina, Voight Bf, Anna Köttgen, Man Li, Olivier Le Bacquer, Bergman Rn, François Pattou, Yvonne Boettcher, Jalal Taneera, Valgerdur Steinthorsdottir, Bielinski Sj, Jian’an Luan, Denis Rybin, Bonnycastle Ll, Kristin Ardlie, Michael Sampson, Buchanan Ta, Lu Qi, Michael N. Weedon, Bumpstead Sj, Inga Prokopenko

, Yurii S. Aulchenko, Benjamin F. Voight, Gabriel J. Crawford, Harald Grallert, Toby Johnson

, Beverley Balkau, Chines Ps, Richard N. Bergman, Niels Grarup

, Suzette J. Bielinski, Collins Fs, Manning Ak, Amélie Bonnefond

, Lori Ll Bonnycastle, Knut Borch-Johnsen, Egan Jm, Yvonne Böttcher, Torben Jørgensen, Eric Brunner, Thomas A. Buchanan, Erdos Mr, Suzannah J. Bumpstead, Jackson Au, Christine Cavalcanti-Proença, Stringham Hm, Forouhi Ng, Guillaume Charpentier, Yii-Der Ida Chen, Claire Levy-Marchal, Peter S. Chines, Fox Cs, Francis S. Collins, Marilyn Cornelis, Kao Wh, Gabriel J. Crawford, Jerome Delplanque, Alex Doney, Goodarzi Mo, C. N. Apalmer, Josephine M. Egan, Michael R. Erdos, Eleftheria Zeggini

, Mathieu Firmann, T. Jùrgensen, Jing Hua Zhao, Nita G. Forouhi, McAteer Jb, Caroline S. Fox, Mark O. Goodarzi, Jürgen Graessler, Mitchell Bd, Aroon Hingorani, Boesgaard Tw, Bo Isomaa, Mohlke Kl, Torben Jorgensen, Glazer Nl, Mika Kivimaki

, Anke Tönjes, Peter Kovacs, Morken Ma, Knut Krohn, Meena Kumari, Palmer Cn, Torsten Lauritzen, Claire Lévy-Marchal, Anke Toenjes, Vladimir Mayor, Sayer Aa, Jarred B. McAteer, Scott Lj, David Meyre, Braxton D. Mitchell, Cornelia Van Duijn, Karen L. Mohlke, G. Consortium, Mario A. Morken, Sharp Sj, Thomas Illig, Narisu Narisu, Siscovick Ds, Colin N. A. Palmer, Ruth Pakyz, H. Erich Wichmann, Smith Nl, Laura Pascoe, C. Duijn, Felicity Payne, Frank B. Hu, Daniel Pearson, Andrew D. Morris, Wolfgang Rathmann, Timothy M. Frayling, Annelli Sandbaek, Swift Aj, Andrew T. Hattersley, Avan Aihie Sayer, T. Sparsù, Laura J. Scott, Valle Tt, Stephen J. Sharp, Unnur Thorsteinsdottir, Eric Sijbrands, Kari Stefansson, Peter Nilsson, Andrew Singleton, Ann-Christine Syvanen, Alan R. Shuldiner, David S. Siscovick, Mark Walker, Nicholas L. Smith, Stefan R. Bornstein, Waterworth Dm, Thomas Sparsø, Peter Schwarz, Amy J. Swift, Zhao Jh, David M. Nathan, Holly Syddall, Consortium Giant, Gudmar Thorleifsson, Johanna Kuusisto, Markku Laakso, Anke Tönjes, Investigators Magic, Cyrus Cooper, Tiinamaija Tuomi, Michael Marmot, Luigi Ferrucci, Jaakko Tuomilehto, Wichmann He, Vincent Mooser, Timo Tt Valle, Michael Stumvoll, Wilson Jf, Ruth J. F. Loos, Gerard Waeber, David Altshuler, Hu Fb, Andrew Walley

, Bruce M. Psaty, Jerome I. Rotter, Eric Boerwinkle, Dawn M. Waterworth, Morris Ad, Torben Hansen, Oluf Pedersen, Frayling Tm, Jose C. Florez, Mark I. McCarthy, Hattersley At, Michael Boehnke, Inês Barroso, Robert Sladek

, Syvänen Ac, Philippe Froguel, James B. Meigs, Shuldiner Ar, Leif Groop, Nicholas J. Wareham, Magic Investigators Giant Consortium, Richard M. Watanabe, Watanabe Rm

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Abstract

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Abstract