Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
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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; Luan, Jian'an; Stringham, Heather M; Prokopenko, Inga; Johnson, Toby; Grarup, Niels; Boesgaard, Trine W; Lecoeur, Cécile; Shrader, Peter; O'Connell, Jeffrey; Ingelsson, Erik; Couper, David J; Rice, Kenneth; Song, Kijoung; Andreasen, Camilla H; Dina, Christian; Köttgen, Anna; Le Bacquer, Olivier; Pattou, François; Taneera, Jalal; Steinthorsdottir, Valgerdur; Rybin, Denis; Ardlie, Kristin; Sampson, Michael; Qi, Lu; van Hoek, Mandy; Weedon, Michael N; Aulchenko, Yurii S; Voight, Benjamin F; Grallert, Harald; Balkau, Beverley; Bergman, Richard N; Borch-Johnsen, Knut; Jørgensen, Torben; Sparsø, Thomas; Hansen, Torben; Pedersen, Oluf; GIANT Consortium.
In: Nature Genetics, Vol. 42, No. 2, 01.02.2010, p. 142-8.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Luan, Jian'an
AU - Stringham, Heather M
AU - Prokopenko, Inga
AU - Johnson, Toby
AU - Grarup, Niels
AU - Boesgaard, Trine W
AU - Lecoeur, Cécile
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, François
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 - Borch-Johnsen, Knut
AU - Jørgensen, Torben
AU - Sparsø, Thomas
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - GIANT Consortium
PY - 2010/2/1
Y1 - 2010/2/1
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 - Adenylate Cyclase
KW - Body Mass Index
KW - Denmark
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Genetic Loci
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Glucose
KW - Glucose Tolerance Test
KW - Humans
KW - Incretins
KW - Insulin
KW - Male
KW - Meta-Analysis as Topic
KW - Polymorphism, Single Nucleotide
KW - Proteins
KW - RNA, Messenger
KW - Receptors, Gastrointestinal Hormone
U2 - 10.1038/ng.521
DO - 10.1038/ng.521
M3 - Journal article
C2 - 20081857
VL - 42
SP - 142
EP - 148
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -
ID: 33507836