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

Richa Saxena; Marie-France Hivert; Claudia Langenberg; Toshiko Tanaka; James S. Pankow; Peter Vollenweider; Valeriya Lyssenko; Nabila Bouatia-Naji; Josee Dupuis; Anne U. Jackson; W. H. Linda Kao; Man Li; Nicole L. Glazer; Alisa K. Manning; Jian'an Luan; Heather M. Stringham; Inga Prokopenko; Toby Johnson; Niels Grarup; Trine W. Boesgaard; Cecile Lecoeur; Peter Shrader; Jeffrey O'Connell; Erik Ingelsson; David J. Couper; Kenneth Rice; Kijoung Song; Camilla H. Andreasen; Christian Dina; Anna Köttgen; Olivier Le Bacquer; Francois Pattou; Jalal Taneera; Valgerdur Steinthorsdottir; Denis Rybin; Kristin Ardlie; Michael Sampson; Lu Qi; Mandy van Hoek; Michael N. Weedon; Yurii S. Aulchenko; Benjamin F. Voight; Harald Grallert; Beverley Balkau; Richard N. Bergman; Suzette J. Bielinski; Amelie Bonnefond; Alex Doney; Colin N. A. Palmer; Andrew D. Morris; GIANT Consortium, MAGIC Investigators

doi:10.1038/ng.521

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

Richa Saxena, Marie-France Hivert, Claudia Langenberg, Toshiko Tanaka, James S. Pankow, Peter Vollenweider, Valeriya Lyssenko, Nabila Bouatia-Naji, Josee Dupuis, Anne U. Jackson, W. H. Linda Kao, Man Li, Nicole L. Glazer, Alisa K. Manning, Jian'an Luan, Heather M. Stringham, Inga Prokopenko, Toby Johnson, Niels Grarup, Trine W. BoesgaardCecile Lecoeur, Peter Shrader, Jeffrey O'Connell, Erik Ingelsson, David J. Couper, Kenneth Rice, Kijoung Song, Camilla H. Andreasen, Christian Dina, Anna Köttgen, Olivier Le Bacquer, Francois Pattou, Jalal Taneera, Valgerdur Steinthorsdottir, Denis Rybin, Kristin Ardlie, Michael Sampson, Lu Qi, Mandy van Hoek, Michael N. Weedon, Yurii S. Aulchenko, Benjamin F. Voight, Harald Grallert, Beverley Balkau, Richard N. Bergman, Suzette J. Bielinski, Amelie Bonnefond, Alex Doney, Colin N. A. Palmer, Andrew D. Morris, GIANT Consortium, MAGIC Investigators

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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	English
Pages (from-to)	142-148
Number of pages	7
Journal	Nature Genetics
Volume	42
Issue number	2
DOIs	https://doi.org/10.1038/ng.521
Publication status	Published - Feb 2010

Keywords

FASTING PLASMA-GLUCOSE
GASTRIC-INHIBITORY POLYPEPTIDE
GLUCAGON-LIKE PEPTIDE-1
BETA-CELL FUNCTION
ASSOCIATION
RISK
RECEPTOR
SENSITIVITY
EXPRESSION
VARIANTS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Saxena, R., Hivert, M.-F., Langenberg, C., Tanaka, T., Pankow, J. S., Vollenweider, P., Lyssenko, V., Bouatia-Naji, N., Dupuis, J., Jackson, A. U., Kao, W. H. L., Li, M., Glazer, N. L., Manning, A. K., Luan, J., Stringham, H. M., Prokopenko, I., Johnson, T., Grarup, N., ... GIANT Consortium, MAGIC Investigators (2010). Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nature Genetics, 42(2), 142-148. https://doi.org/10.1038/ng.521

@article{b65a218a0fe5415d82ce0dbe640b47c5,

title = "Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge",

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)).",

keywords = "FASTING PLASMA-GLUCOSE, GASTRIC-INHIBITORY POLYPEPTIDE, GLUCAGON-LIKE PEPTIDE-1, BETA-CELL FUNCTION, ASSOCIATION, RISK, RECEPTOR, SENSITIVITY, EXPRESSION, VARIANTS",

author = "Richa Saxena and Marie-France Hivert and Claudia Langenberg and Toshiko Tanaka and Pankow, {James S.} and Peter Vollenweider and Valeriya Lyssenko and Nabila Bouatia-Naji and Josee Dupuis and Jackson, {Anne U.} and Kao, {W. H. Linda} and Man Li and Glazer, {Nicole L.} and Manning, {Alisa K.} and Jian'an Luan and Stringham, {Heather M.} and Inga Prokopenko and Toby Johnson and Niels Grarup and Boesgaard, {Trine W.} and Cecile Lecoeur and Peter Shrader and Jeffrey O'Connell and Erik Ingelsson and Couper, {David J.} and Kenneth Rice and Kijoung Song and Andreasen, {Camilla H.} and Christian Dina and Anna K{\"o}ttgen and {Le Bacquer}, Olivier and Francois Pattou and Jalal Taneera and Valgerdur Steinthorsdottir and Denis Rybin and Kristin Ardlie and Michael Sampson and Lu Qi and {van Hoek}, Mandy and Weedon, {Michael N.} and Aulchenko, {Yurii S.} and Voight, {Benjamin F.} and Harald Grallert and Beverley Balkau and Bergman, {Richard N.} and Bielinski, {Suzette J.} and Amelie Bonnefond and Alex Doney and Palmer, {Colin N. A.} and Morris, {Andrew D.} and {GIANT Consortium, MAGIC Investigators}",

year = "2010",

month = feb,

doi = "10.1038/ng.521",

language = "English",

volume = "42",

pages = "142--148",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Saxena, R, Hivert, M-F, 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, K, Andreasen, CH, Dina, C, Köttgen, 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, Doney, A , Palmer, CNA, Morris, AD & GIANT Consortium, MAGIC Investigators 2010, 'Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge', Nature Genetics, vol. 42, no. 2, pp. 142-148. 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, 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, Josee

AU - Jackson, Anne U.

AU - Kao, W. H. Linda

AU - Li, Man

AU - Glazer, Nicole L.

AU - Manning, Alisa K.

AU - Luan, Jian'an

AU - Stringham, Heather M.

AU - Prokopenko, Inga

AU - Johnson, Toby

AU - Grarup, Niels

AU - Boesgaard, Trine W.

AU - Lecoeur, Cecile

AU - Shrader, Peter

AU - O'Connell, 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 - Le Bacquer, Olivier

AU - Pattou, Francois

AU - Taneera, Jalal

AU - Steinthorsdottir, Valgerdur

AU - Rybin, Denis

AU - Ardlie, Kristin

AU - Sampson, Michael

AU - Qi, Lu

AU - van Hoek, Mandy

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 - Doney, Alex

AU - Palmer, Colin N. A.

AU - Morris, Andrew D.

AU - GIANT Consortium, MAGIC Investigators

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, 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)).

KW - FASTING PLASMA-GLUCOSE

KW - GASTRIC-INHIBITORY POLYPEPTIDE

KW - GLUCAGON-LIKE PEPTIDE-1

KW - BETA-CELL FUNCTION

KW - ASSOCIATION

KW - RISK

KW - RECEPTOR

KW - SENSITIVITY

KW - EXPRESSION

KW - VARIANTS

U2 - 10.1038/ng.521

DO - 10.1038/ng.521

M3 - Article

C2 - 20081857

SN - 1061-4036

VL - 42

SP - 142

EP - 148

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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