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

Saxena, Richa; Hivert, Marie-France; Langenberg, Claudia; Tanaka, Toshiko; Pankow, James S.; Vollenweider, Peter; Lyssenko, Valeriya LU ; Bouatia-Naji, Nabila; Dupuis, Josee and Jackson, Anne U., et al. (2010) In Nature Genetics 42(2). p.75-142
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... (More)
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)). (Less)
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Nature Genetics
volume
42
issue
2
pages
75 - 142
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Nature Publishing Group
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  • wos:000274084400011
  • scopus:75749091912
ISSN
1546-1718
DOI
10.1038/ng.521
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English
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yes
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7c7e3cf9-9e3d-4371-9139-74000ff2b213 (old id 1569874)
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2010-03-17 09:37:46
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2018-06-24 04:10:29
@article{7c7e3cf9-9e3d-4371-9139-74000ff2b213,
  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       = {Saxena, Richa and Hivert, Marie-France and Langenberg, Claudia and Tanaka, Toshiko and Pankow, James S. and Vollenweider, Peter and Lyssenko, Valeriya and Bouatia-Naji, Nabila and Dupuis, Josee and Jackson, Anne U. and Kao, W. H. Linda and Li, Man and Glazer, Nicole L. and Manning, Alisa K. and Luan, Jian'an and Stringham, Heather M. and Prokopenko, Inga and Johnson, Toby and Grarup, Niels and Boesgaard, Trine W. and Lecoeur, Cecile and Shrader, Peter and O'Connell, Jeffrey and Ingelsson, Erik and Couper, David J. and Rice, Kenneth and Song, Kijoung and Andreasen, Camilla H. and Dina, Christian and Koettgen, Anna and Le Bacquer, Olivier and Pattou, Francois and Taneera, Jalal and Steinthorsdottir, Valgerdur and Rybin, Denis and Ardlie, Kristin and Sampson, Michael and Qi, Lu and van Hoek, Mandy and Weedon, Michael N. and Aulchenko, Yurii S. and Voight, Benjamin F. and Grallert, Harald and Balkau, Beverley and Bergman, Richard N. and Bielinski, Suzette J. and Bonnefond, Amelie and Bonnycastle, Lori L. and Borch-Johnsen, Knut and Boettcher, Yvonne and Brunner, Eric and Buchanan, Thomas A. and Bumpstead, Suzannah J. and Cavalcanti-Proenca, Christine and Charpentier, Guillaume and Chen, Yii-Der Ida and Chines, Peter S. and Collins, Francis S. and Cornelis, Marilyn and Crawford, Gabriel J. and Delplanque, Jerome and Doney, Alex and Egan, Josephine M. and Erdos, Michael R. and Firmann, Mathieu and Forouhi, Nita G. and Fox, Caroline S. and Goodarzi, Mark O. and Graessler, Juergen and Hingorani, Aroon and Isomaa, Bo and Jorgensen, Torben and Kivimaki, Mika and Kovacs, Peter and Krohn, Knut and Kumari, Meena and Lauritzen, Torsten and Levy-Marchal, Claire and Mayor, Vladimir and McAteer, Jarred B. and Meyre, David and Mitchell, Braxton D. and Mohlke, Karen L. and Morken, Mario A. and Narisu, Narisu and Palmer, Colin N. A. and Pakyz, Ruth and Pascoe, Laura and Payne, Felicity and Pearson, Daniel and Rathmann, Wolfgang and Sandbaek, Annelli and Sayer, Avan Aihie and Scott, Laura J. and Sharp, Stephen J. and Sijbrands, Eric and Singleton, Andrew and Siscovick, David S. and Smith, Nicholas L. and Sparso, Thomas and Swift, Amy J. and Syddall, Holly and Thorleifsson, Gudmar and Toenjes, Anke and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Valle, Timo T. and Waeber, Gerard and Walley, Andrew and Waterworth, Dawn M. and Zeggini, Eleftheria and Zhao, Jing Hua and Illig, Thomas and Wichmann, H. Erich and Wilson, James F. and van Duijn, Cornelia and Hu, Frank B. and Morris, Andrew D. and Frayling, Timothy M. and Hattersley, Andrew T. and Thorsteinsdottir, Unnur and Stefansson, Kari and Nilsson, Peter and Syvanen, Ann-Christine and Shuldiner, Alan R. and Walker, Mark and Bornstein, Stefan R. and Schwarz, Peter and Williams, Gordon H. and Nathan, David M. and Kuusisto, Johanna and Laakso, Markku and Cooper, Cyrus and Marmot, Michael and Ferrucci, Luigi and Mooser, Vincent and Stumvoll, Michael and Loos, Ruth J. F. and Altshuler, David and Psaty, Bruce M. and Rotter, Jerome I. and Boerwinkle, Eric and Hansen, Torben and Pedersen, Oluf and Florez, Jose C. and McCarthy, Mark I. and Boehnke, Michael and Barroso, Ines and Sladek, Robert and Froguel, Philippe and Meigs, James B. and Groop, Leif and Wareham, Nicholas J. and Watanabe, Richard M.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {2},
  pages        = {75--142},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge},
  url          = {http://dx.doi.org/10.1038/ng.521},
  volume       = {42},
  year         = {2010},
}