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, Β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10 15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10 17; ratio of insulin to glucose area under the curve, P = 1.3 × 10 16) and diminished incretin effect (n = 804; P = 4.3 × 10 4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10 16), VPS13C (rs17271305, P = 4.1 × 10 8), GCKR (rs1260326, P = 7.1 × 10 11) and TCF7L2 (rs7903146, P = 4.2 × 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 × 10 18).
Original language | English (US) |
---|---|
Pages (from-to) | 142-148 |
Number of pages | 7 |
Journal | Nature Genetics |
Volume | 42 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2010 |
ASJC Scopus subject areas
- Genetics
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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; Bouatia-Naji, Nabila; Dupuis, Josée; Jackson, Anne U.; Kao, W. H Linda; Li, Man; Glazer, Nicole L.; Manning, Alisa K.; Anluan, Jian; Stringham, Heather M.; Prokopenko, Inga; Johnson, Toby; Grarup, Niels; Boesgaard, Trine W.; Lecoeur, Cécile; Shrader, Peter; Oconnell, Jeffrey; Ingelsson, Erik; Couper, David J.; Rice, Kenneth; Song, Kijoung; Andreasen, Camilla H.; Dina, Christian; KöTTGEN, Anna; Bacquer, Olivier Le; Pattou, François; Taneera, Jalal; Steinthorsdottir, Valgerdur; Rybin, Denis; Ardlie, Kristin; Sampson, Michael; Qi, Lu; Hoek, Mandy Van; Weedon, Michael N.; Aulchenko, Yurii S.; Voight, Benjamin F.; Grallert, Harald; Balkau, Beverley; Bergman, Richard N.; Bielinski, Suzette J.; Bonnefond, Amelie; Bonnycastle, Lori L.; Borch-Johnsen, Knut; BöTTCHER, Yvonne; Brunner, Eric; Buchanan, Thomas A.; Bumpstead, Suzannah J.; Cavalcanti-Proença, Christine; Charpentier, Guillaume; Chen, Yii Der Ida; Chines, Peter S.; Collins, Francis S.; Cornelis, Marilyn; Crawford, Gabriel J.; Delplanque, Jerome; Doney, Alex; Egan, Josephine M.; Erdos, Michael R.; Firmann, Mathieu; Forouhi, Nita G.; Fox, Caroline S.; Goodarzi, Mark O.; Graessler, Jürgen; Hingorani, Aroon; Isomaa, Bo; Jørgensen, Torben; Kivimaki, Mika; Kovacs, Peter; Krohn, Knut; Kumari, Meena; Lauritzen, Torsten; Lévy-Marchal, Claire; Mayor, Vladimir; McAteer, Jarred B.; Meyre, David; Mitchell, Braxton D.; Mohlke, Karen L.; Morken, Mario A.; Narisu, Narisu; Apalmer, Colin N.; Pakyz, Ruth; Pascoe, Laura; Payne, Felicity; Pearson, Daniel; Rathmann, Wolfgang; Sandbaek, Annelli; Sayer, Avan Aihie; Scott, Laura J.; Sharp, Stephen J.; Sijbrands, Eric; Singleton, Andrew; Siscovick, David S.; Smith, Nicholas L.; Sparsø, Thomas; Swift, Amy J.; Syddall, Holly; Thorleifsson, Gudmar; TöNJES, Anke; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Valle, Timo T.; Waeber, Gérard; Walley, Andrew; Waterworth, Dawn M.; Zeggini, Eleftheria; Zhao, Jing Hua; Consortium, Giant; Illig, Thomas; Wichmann, H. Erich; Wilson, James F.; Duijn, Cornelia Van; Hu, Frank B.; Morris, Andrew D.; Frayling, Timothy M.; Hattersley, Andrew T.; Thorsteinsdottir, Unnur; Stefansson, Kari; Nilsson, Peter; Syvänen, Ann Christine; Shuldiner, Alan R.; Walker, Mark; Bornstein, Stefan R.; Schwarz, Peter; Williams, Gordon H.; Nathan, David M.; Kuusisto, Johanna; Laakso, Markku; Cooper, Cyrus; Marmot, Michael; Ferrucci, Luigi; Mooser, Vincent; Stumvoll, Michael; Loos, Ruth J F; Altshuler, David; Psaty, Bruce M.; Rotter, Jerome I.; Boerwinkle, Eric; Hansen, Torben; Pedersen, Oluf; Florez, Jose C.; McCarthy, Mark I.; Boehnke, Michael; Barroso, Inês; Sladek, Robert; Froguel, Philippe; Meigs, James B.; Groop, Leif; Wareham, Nicholas J.; Watanabe, Richard M.
In: Nature Genetics, Vol. 42, No. 2, 02.2010, p. 142-148.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
AU - Saxena, Richa
AU - Hivert, Marie France
AU - Langenberg, Claudia
AU - Tanaka, Toshiko
AU - Pankow, James S.
AU - Vollenweider, Peter
AU - Lyssenko, Valeriya
AU - Bouatia-Naji, Nabila
AU - Dupuis, Josée
AU - Jackson, Anne U.
AU - Kao, W. H Linda
AU - Li, Man
AU - Glazer, Nicole L.
AU - Manning, Alisa K.
AU - Anluan, Jian
AU - Stringham, Heather M.
AU - Prokopenko, Inga
AU - Johnson, Toby
AU - Grarup, Niels
AU - Boesgaard, Trine W.
AU - Lecoeur, Cécile
AU - Shrader, Peter
AU - Oconnell, Jeffrey
AU - Ingelsson, Erik
AU - Couper, David J.
AU - Rice, Kenneth
AU - Song, Kijoung
AU - Andreasen, Camilla H.
AU - Dina, Christian
AU - KöTTGEN, Anna
AU - Bacquer, Olivier Le
AU - Pattou, François
AU - Taneera, Jalal
AU - Steinthorsdottir, Valgerdur
AU - Rybin, Denis
AU - Ardlie, Kristin
AU - Sampson, Michael
AU - Qi, Lu
AU - Hoek, Mandy Van
AU - Weedon, Michael N.
AU - Aulchenko, Yurii S.
AU - Voight, Benjamin F.
AU - Grallert, Harald
AU - Balkau, Beverley
AU - Bergman, Richard N.
AU - Bielinski, Suzette J.
AU - Bonnefond, Amelie
AU - Bonnycastle, Lori L.
AU - Borch-Johnsen, Knut
AU - BöTTCHER, Yvonne
AU - Brunner, Eric
AU - Buchanan, Thomas A.
AU - Bumpstead, Suzannah J.
AU - Cavalcanti-Proença, Christine
AU - Charpentier, Guillaume
AU - Chen, Yii Der Ida
AU - Chines, Peter S.
AU - Collins, Francis S.
AU - Cornelis, Marilyn
AU - Crawford, Gabriel J.
AU - Delplanque, Jerome
AU - Doney, Alex
AU - Egan, Josephine M.
AU - Erdos, Michael R.
AU - Firmann, Mathieu
AU - Forouhi, Nita G.
AU - Fox, Caroline S.
AU - Goodarzi, Mark O.
AU - Graessler, Jürgen
AU - Hingorani, Aroon
AU - Isomaa, Bo
AU - Jørgensen, Torben
AU - Kivimaki, Mika
AU - Kovacs, Peter
AU - Krohn, Knut
AU - Kumari, Meena
AU - Lauritzen, Torsten
AU - Lévy-Marchal, Claire
AU - Mayor, Vladimir
AU - McAteer, Jarred B.
AU - Meyre, David
AU - Mitchell, Braxton D.
AU - Mohlke, Karen L.
AU - Morken, Mario A.
AU - Narisu, Narisu
AU - Apalmer, Colin N.
AU - Pakyz, Ruth
AU - Pascoe, Laura
AU - Payne, Felicity
AU - Pearson, Daniel
AU - Rathmann, Wolfgang
AU - Sandbaek, Annelli
AU - Sayer, Avan Aihie
AU - Scott, Laura J.
AU - Sharp, Stephen J.
AU - Sijbrands, Eric
AU - Singleton, Andrew
AU - Siscovick, David S.
AU - Smith, Nicholas L.
AU - Sparsø, Thomas
AU - Swift, Amy J.
AU - Syddall, Holly
AU - Thorleifsson, Gudmar
AU - TöNJES, Anke
AU - Tuomi, Tiinamaija
AU - Tuomilehto, Jaakko
AU - Valle, Timo T.
AU - Waeber, Gérard
AU - Walley, Andrew
AU - Waterworth, Dawn M.
AU - Zeggini, Eleftheria
AU - Zhao, Jing Hua
AU - Consortium, Giant
AU - Illig, Thomas
AU - Wichmann, H. Erich
AU - Wilson, James F.
AU - Duijn, Cornelia Van
AU - Hu, Frank B.
AU - Morris, Andrew D.
AU - Frayling, Timothy M.
AU - Hattersley, Andrew T.
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
AU - Nilsson, Peter
AU - Syvänen, Ann Christine
AU - Shuldiner, Alan R.
AU - Walker, Mark
AU - Bornstein, Stefan R.
AU - Schwarz, Peter
AU - Williams, Gordon H.
AU - Nathan, David M.
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Cooper, Cyrus
AU - Marmot, Michael
AU - Ferrucci, Luigi
AU - Mooser, Vincent
AU - Stumvoll, Michael
AU - Loos, Ruth J F
AU - Altshuler, David
AU - Psaty, Bruce M.
AU - Rotter, Jerome I.
AU - Boerwinkle, Eric
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Florez, Jose C.
AU - McCarthy, Mark I.
AU - Boehnke, Michael
AU - Barroso, Inês
AU - Sladek, Robert
AU - Froguel, Philippe
AU - Meigs, James B.
AU - Groop, Leif
AU - Wareham, Nicholas J.
AU - Watanabe, Richard M.
N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - 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, Β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10 15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10 17; ratio of insulin to glucose area under the curve, P = 1.3 × 10 16) and diminished incretin effect (n = 804; P = 4.3 × 10 4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10 16), VPS13C (rs17271305, P = 4.1 × 10 8), GCKR (rs1260326, P = 7.1 × 10 11) and TCF7L2 (rs7903146, P = 4.2 × 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 × 10 18).
AB - 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, Β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10 15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10 17; ratio of insulin to glucose area under the curve, P = 1.3 × 10 16) and diminished incretin effect (n = 804; P = 4.3 × 10 4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10 16), VPS13C (rs17271305, P = 4.1 × 10 8), GCKR (rs1260326, P = 7.1 × 10 11) and TCF7L2 (rs7903146, P = 4.2 × 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 × 10 18).
UR - http://www.scopus.com/inward/record.url?scp=75749091912&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75749091912&partnerID=8YFLogxK
U2 - 10.1038/ng.521
DO - 10.1038/ng.521
M3 - Article
C2 - 20081857
AN - SCOPUS:75749091912
VL - 42
SP - 142
EP - 148
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -