Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
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, ? (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).
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17 February 2010
Saxena, Richa
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Mitchell, Braxton D.
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Syddall, Holly
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Thorleifsson, Gudmar
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Zhao, Jing Hua
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consortium, GIANT
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Stefansson, Kari
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Nilsson, Peter
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Bornstein, Stefan R.
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Nathan, David M.
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Stumvoll, Michael
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Altshuler, David
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Florez, Jose C.
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Mc Carthy, Mark I.
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Boehnke, Michael
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Barroso, Inês
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Sladek, Robert
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Froguel, Philippe
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Meigs, James B.
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Groop, Leif
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Wareham, Nicholas J.
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Watanabe, Richard M.
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