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

R Saxena; MF Hivert; C Langenberg; T Tanaka; JS Pankow; P Vollenweider; V Lyssenko; N Bouatia-Naji; J Dupuis; AU Jackson; WHL Kao; M Li; NL Glazer; AK Manning; J Luan; HM Stringham; I Prokopenko; T Johnson; N Grarup; TW Boesgaard; C Lecoeur; P Shrader; J O'Connell; E Ingelsson; DJ Couper; K Rice; KJ Song; CH Andreasen; C Dina; A Kottgen; O Le Bacquer; F Pattou; J Taneera; V Steinthorsdottir; D Rybin; K Ardlie; M Sampson; L Qi; Mandy van Hoek; MN Weedon; YS Aulchenko; BF Voight; H Grallert; B Balkau; RN Bergman; SJ Bielinski; A Bonnefond; LL Bonnycastle; K Borch-Johnsen; Y Boettcher; E Brunner; TA Buchanan; SJ Bumpstead; C Cavalcanti-Proenca; G Charpentier; YDI Chen; PS Chines; FS Collins; M Cornelis; GJ Crawford; J Delplanque; A Doney; JM Egan; MR Erdos; M Firmann; NG Forouhi; CS Fox; MO Goodarzi; J Graessler; A Hingorani; B Isomaa; T Jorgensen; M Kivimaki; P Kovacs; K Krohn; M Kumari; T Lauritzen; C Levy-Marchal; V Mayor; JB McAteer; D Meyre; BD Mitchell; KL Mohlke; MA Morken; N Narisu; CNA Palmer; R Pakyz; L Pascoe; F Payne; D Pearson; W Rathmann; A Sandbaek; AA Sayer; LJ Scott; SJ Sharp; E.J.G. Sijbrands; A Singleton; DS Siscovick; NL Smith; T Sparso; AJ Swift; H Syddall; G Thorleifsson; A Tonjes; T Tuomi; J Tuomilehto; TT Valle; G Waeber; A Walley; DM Waterworth; E Zeggini; JH Zhao; T Illig; HE Wichmann; JF Wilson; Cornelia Duijn; FB Hu; AD Morris; TM Frayling; AT Hattersley; U Thorsteinsdottir; K Stefansson; P Nilsson; AC Syvanen; AR Shuldiner; M Walker; SR Bornstein; P Schwarz; GH Williams; DM Nathan; J Kuusisto; M Laakso; C Cooper; M Marmot; L Ferrucci; V Mooser; M Stumvoll; RJF Loos; D Altshuler; BM Psaty; JI Rotter; E Boerwinkle; T Hansen; O Pedersen; JC Florez; MI McCarthy; M Boehnke; I Barroso; R Sladek; P Froguel; JB Meigs; L Groop; NJ Wareham; RM Watanabe

doi:10.1038/ng.521

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

R Saxena, MF Hivert, C Langenberg, T Tanaka, JS Pankow, P Vollenweider, V Lyssenko, N Bouatia-Naji, J Dupuis, AU Jackson, WHL Kao, M Li, NL Glazer, AK Manning, J Luan, HM Stringham, I Prokopenko, T Johnson, N Grarup, TW BoesgaardC Lecoeur, P Shrader, J O'Connell, E Ingelsson, DJ Couper, K Rice, KJ Song, CH Andreasen, C Dina, A Kottgen, O Le Bacquer, F Pattou, J Taneera, V Steinthorsdottir, D Rybin, K Ardlie, M Sampson, L Qi, Mandy van Hoek, MN Weedon, YS Aulchenko, BF Voight, H Grallert, B Balkau, RN Bergman, SJ Bielinski, A Bonnefond, LL Bonnycastle, K Borch-Johnsen, Y Boettcher, E Brunner, TA Buchanan, SJ Bumpstead, C Cavalcanti-Proenca, G Charpentier, YDI Chen, PS Chines, FS Collins, M Cornelis, GJ Crawford, J Delplanque, A Doney, JM Egan, MR Erdos, M Firmann, NG Forouhi, CS Fox, MO Goodarzi, J Graessler, A Hingorani, B Isomaa, T Jorgensen, M Kivimaki, P Kovacs, K Krohn, M Kumari, T Lauritzen, C Levy-Marchal, V Mayor, JB McAteer, D Meyre, BD Mitchell, KL Mohlke, MA Morken, N Narisu, CNA Palmer, R Pakyz, L Pascoe, F Payne, D Pearson, W Rathmann, A Sandbaek, AA Sayer, LJ Scott, SJ Sharp, E.J.G. Sijbrands, A Singleton, DS Siscovick, NL Smith, T Sparso, AJ Swift, H Syddall, G Thorleifsson, A Tonjes, T Tuomi, J Tuomilehto, TT Valle, G Waeber, A Walley, DM Waterworth, E Zeggini, JH Zhao, T Illig, HE Wichmann, JF Wilson, Cornelia Duijn, FB Hu, AD Morris, TM Frayling, AT Hattersley, U Thorsteinsdottir, K Stefansson, P Nilsson, AC Syvanen, AR Shuldiner, M Walker, SR Bornstein, P Schwarz, GH Williams, DM Nathan, J Kuusisto, M Laakso, C Cooper, M Marmot, L Ferrucci, V Mooser, M Stumvoll, RJF Loos, D Altshuler, BM Psaty, JI Rotter, E Boerwinkle, T Hansen, O Pedersen, JC Florez, MI McCarthy, M Boehnke, I Barroso, R Sladek, P Froguel, JB Meigs, L Groop, NJ Wareham, RM Watanabe

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

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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)).

Original language	Undefined/Unknown
Pages (from-to)	142-U75
Journal	Nature Genetics
Volume	42
Issue number	2
DOIs	https://doi.org/10.1038/ng.521
Publication status	Published - 2010

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10.1038/ng.521

http://hdl.handle.net/1765/28331

Cite this

Saxena, R., Hivert, MF., Langenberg, C., Tanaka, T., Pankow, JS., Vollenweider, P., Lyssenko, V., Bouatia-Naji, N., Dupuis, J., Jackson, AU., Kao, WHL., Li, M., Glazer, NL., Manning, AK., Luan, J., Stringham, HM., Prokopenko, I., Johnson, T., Grarup, N., ... Watanabe, RM. (2010). Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nature Genetics, 42(2), 142-U75. https://doi.org/10.1038/ng.521

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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)).",

author = "R Saxena and MF Hivert and C Langenberg and T Tanaka and JS Pankow and P Vollenweider and V Lyssenko and N Bouatia-Naji and J Dupuis and AU Jackson and WHL Kao and M Li and NL Glazer and AK Manning and J Luan and HM Stringham and I Prokopenko and T Johnson and N Grarup and TW Boesgaard and C Lecoeur and P Shrader and J O'Connell and E Ingelsson and DJ Couper and K Rice and KJ Song and CH Andreasen and C Dina and A Kottgen and {Le Bacquer}, O and F Pattou and J Taneera and V Steinthorsdottir and D Rybin and K Ardlie and M Sampson and L Qi and {van Hoek}, Mandy and MN Weedon and YS Aulchenko and BF Voight and H Grallert and B Balkau and RN Bergman and SJ Bielinski and A Bonnefond and LL Bonnycastle and K Borch-Johnsen and Y Boettcher and E Brunner and TA Buchanan and SJ Bumpstead and C Cavalcanti-Proenca and G Charpentier and YDI Chen and PS Chines and FS Collins and M Cornelis and GJ Crawford and J Delplanque and A Doney and JM Egan and MR Erdos and M Firmann and NG Forouhi and CS Fox and MO Goodarzi and J Graessler and A Hingorani and B Isomaa and T Jorgensen and M Kivimaki and P Kovacs and K Krohn and M Kumari and T Lauritzen and C Levy-Marchal and V Mayor and JB McAteer and D Meyre and BD Mitchell and KL Mohlke and MA Morken and N Narisu and CNA Palmer and R Pakyz and L Pascoe and F Payne and D Pearson and W Rathmann and A Sandbaek and AA Sayer and LJ Scott and SJ Sharp and E.J.G. Sijbrands and A Singleton and DS Siscovick and NL Smith and T Sparso and AJ Swift and H Syddall and G Thorleifsson and A Tonjes and T Tuomi and J Tuomilehto and TT Valle and G Waeber and A Walley and DM Waterworth and E Zeggini and JH Zhao and T Illig and HE Wichmann and JF Wilson and Cornelia Duijn and FB Hu and AD Morris and TM Frayling and AT Hattersley and U Thorsteinsdottir and K Stefansson and P Nilsson and AC Syvanen and AR Shuldiner and M Walker and SR Bornstein and P Schwarz and GH Williams and DM Nathan and J Kuusisto and M Laakso and C Cooper and M Marmot and L Ferrucci and V Mooser and M Stumvoll and RJF Loos and D Altshuler and BM Psaty and JI Rotter and E Boerwinkle and T Hansen and O Pedersen and JC Florez and MI McCarthy and M Boehnke and I Barroso and R Sladek and P Froguel and JB Meigs and L Groop and NJ Wareham and RM Watanabe",

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doi = "10.1038/ng.521",

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Saxena, R, Hivert, MF, Langenberg, C, Tanaka, T, Pankow, JS, Vollenweider, P, Lyssenko, V, Bouatia-Naji, N, Dupuis, J, Jackson, AU, Kao, WHL, Li, M, Glazer, NL, Manning, AK, Luan, J, Stringham, HM, Prokopenko, I, Johnson, T, Grarup, N, Boesgaard, TW, Lecoeur, C, Shrader, P, O'Connell, J, Ingelsson, E, Couper, DJ, Rice, K, Song, KJ, Andreasen, CH, Dina, C, Kottgen, A, Le Bacquer, O, Pattou, F, Taneera, J, Steinthorsdottir, V, Rybin, D, Ardlie, K, Sampson, M, Qi, L, van Hoek, M, Weedon, MN, Aulchenko, YS, Voight, BF, Grallert, H, Balkau, B, Bergman, RN, Bielinski, SJ, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Boettcher, Y, Brunner, E, Buchanan, TA, Bumpstead, SJ, Cavalcanti-Proenca, C, Charpentier, G, Chen, YDI, Chines, PS, Collins, FS, Cornelis, M, Crawford, GJ, Delplanque, J, Doney, A, Egan, JM, Erdos, MR, Firmann, M, Forouhi, NG, Fox, CS, Goodarzi, MO, Graessler, J, Hingorani, A, Isomaa, B, Jorgensen, T, Kivimaki, M, Kovacs, P, Krohn, K, Kumari, M, Lauritzen, T, Levy-Marchal, C, Mayor, V, McAteer, JB, Meyre, D, Mitchell, BD, Mohlke, KL, Morken, MA, Narisu, N, Palmer, CNA, Pakyz, R, Pascoe, L, Payne, F, Pearson, D, Rathmann, W, Sandbaek, A, Sayer, AA, Scott, LJ, Sharp, SJ, Sijbrands, EJG, Singleton, A, Siscovick, DS, Smith, NL, Sparso, T, Swift, AJ, Syddall, H, Thorleifsson, G, Tonjes, A, Tuomi, T, Tuomilehto, J, Valle, TT, Waeber, G, Walley, A, Waterworth, DM, Zeggini, E, Zhao, JH, Illig, T, Wichmann, HE, Wilson, JF, Duijn, C, Hu, FB, Morris, AD, Frayling, TM, Hattersley, AT, Thorsteinsdottir, U, Stefansson, K, Nilsson, P, Syvanen, AC, Shuldiner, AR, Walker, M, Bornstein, SR, Schwarz, P, Williams, GH, Nathan, DM, Kuusisto, J, Laakso, M, Cooper, C, Marmot, M, Ferrucci, L, Mooser, V, Stumvoll, M, Loos, RJF, Altshuler, D, Psaty, BM, Rotter, JI, Boerwinkle, E, Hansen, T, Pedersen, O, Florez, JC, McCarthy, MI, Boehnke, M, Barroso, I, Sladek, R, Froguel, P, Meigs, JB, Groop, L, Wareham, NJ & Watanabe, RM 2010, 'Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge', Nature Genetics, vol. 42, no. 2, pp. 142-U75. https://doi.org/10.1038/ng.521

TY - JOUR

T1 - Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

AU - Saxena, R

AU - Hivert, MF

AU - Langenberg, C

AU - Tanaka, T

AU - Pankow, JS

AU - Vollenweider, P

AU - Lyssenko, V

AU - Bouatia-Naji, N

AU - Dupuis, J

AU - Jackson, AU

AU - Kao, WHL

AU - Li, M

AU - Glazer, NL

AU - Manning, AK

AU - Luan, J

AU - Stringham, HM

AU - Prokopenko, I

AU - Johnson, T

AU - Grarup, N

AU - Boesgaard, TW

AU - Lecoeur, C

AU - Shrader, P

AU - O'Connell, J

AU - Ingelsson, E

AU - Couper, DJ

AU - Rice, K

AU - Song, KJ

AU - Andreasen, CH

AU - Dina, C

AU - Kottgen, A

AU - Le Bacquer, O

AU - Pattou, F

AU - Taneera, J

AU - Steinthorsdottir, V

AU - Rybin, D

AU - Ardlie, K

AU - Sampson, M

AU - Qi, L

AU - van Hoek, Mandy

AU - Weedon, MN

AU - Aulchenko, YS

AU - Voight, BF

AU - Grallert, H

AU - Balkau, B

AU - Bergman, RN

AU - Bielinski, SJ

AU - Bonnefond, A

AU - Bonnycastle, LL

AU - Borch-Johnsen, K

AU - Boettcher, Y

AU - Brunner, E

AU - Buchanan, TA

AU - Bumpstead, SJ

AU - Cavalcanti-Proenca, C

AU - Charpentier, G

AU - Chen, YDI

AU - Chines, PS

AU - Collins, FS

AU - Cornelis, M

AU - Crawford, GJ

AU - Delplanque, J

AU - Doney, A

AU - Egan, JM

AU - Erdos, MR

AU - Firmann, M

AU - Forouhi, NG

AU - Fox, CS

AU - Goodarzi, MO

AU - Graessler, J

AU - Hingorani, A

AU - Isomaa, B

AU - Jorgensen, T

AU - Kivimaki, M

AU - Kovacs, P

AU - Krohn, K

AU - Kumari, M

AU - Lauritzen, T

AU - Levy-Marchal, C

AU - Mayor, V

AU - McAteer, JB

AU - Meyre, D

AU - Mitchell, BD

AU - Mohlke, KL

AU - Morken, MA

AU - Narisu, N

AU - Palmer, CNA

AU - Pakyz, R

AU - Pascoe, L

AU - Payne, F

AU - Pearson, D

AU - Rathmann, W

AU - Sandbaek, A

AU - Sayer, AA

AU - Scott, LJ

AU - Sharp, SJ

AU - Sijbrands, E.J.G.

AU - Singleton, A

AU - Siscovick, DS

AU - Smith, NL

AU - Sparso, T

AU - Swift, AJ

AU - Syddall, H

AU - Thorleifsson, G

AU - Tonjes, A

AU - Tuomi, T

AU - Tuomilehto, J

AU - Valle, TT

AU - Waeber, G

AU - Walley, A

AU - Waterworth, DM

AU - Zeggini, E

AU - Zhao, JH

AU - Illig, T

AU - Wichmann, HE

AU - Wilson, JF

AU - Duijn, Cornelia

AU - Hu, FB

AU - Morris, AD

AU - Frayling, TM

AU - Hattersley, AT

AU - Thorsteinsdottir, U

AU - Stefansson, K

AU - Nilsson, P

AU - Syvanen, AC

AU - Shuldiner, AR

AU - Walker, M

AU - Bornstein, SR

AU - Schwarz, P

AU - Williams, GH

AU - Nathan, DM

AU - Kuusisto, J

AU - Laakso, M

AU - Cooper, C

AU - Marmot, M

AU - Ferrucci, L

AU - Mooser, V

AU - Stumvoll, M

AU - Loos, RJF

AU - Altshuler, D

AU - Psaty, BM

AU - Rotter, JI

AU - Boerwinkle, E

AU - Hansen, T

AU - Pedersen, O

AU - Florez, JC

AU - McCarthy, MI

AU - Boehnke, M

AU - Barroso, I

AU - Sladek, R

AU - Froguel, P

AU - Meigs, JB

AU - Groop, L

AU - Wareham, NJ

AU - Watanabe, RM

PY - 2010

Y1 - 2010

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, 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)).

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, 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)).

U2 - 10.1038/ng.521

DO - 10.1038/ng.521

M3 - Article

C2 - 20081857

SN - 1061-4036

VL - 42

SP - 142-U75

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -