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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.* ; Boesgaard, T.W.* ; Lecoeur, C.* ; Shrader, P.* ; O'Connell, J.* ; Ingelsson, E.* ; Couper, D.J.* ; Rice, K.* ; Song, K.J.* ; Andreasen, C.H.* ; 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, M.N.* ; Aulchenko, Y.S.* ; Voight, B.F.* ; Grallert, H. ; Balkau, B.* ; Bergman, R.N.* ; Bielinski, S.J.* ; Bonnefond, A.* ; Bonnycastle, L.L.* ; Borch-Johnsen, K.* ; Böttcher, Y.* ; Brunner, E.* ; Buchanan, T.A.* ; Bumpstead, S.J.* ; Cavalcanti-Proença, C.* ; Charpentier, G.* ; Chen, Y.D.I.* ; Chines, P.S.* ; Collins, F.S.* ; Cornelis, M.* ; Crawford, G.J.* ; Delplanque, J.* ; Doney, A.* ; Egan, J.M.* ; Erdos, M.R.* ; Firmann, M.* ; Forouhi, N.G.* ; Fox, C.S.* ; Goodarzi, M.O.* ; Graessler, J.* ; Hingorani, A.* ; Isomaa, B.* ; Jørgensen, T.* ; Kivimaki, M.* ; Kovacs, P.* ; Krohn, K.* ; Kumari, M.* ; Lauritzen, T.* ; Lévy-Marchal, C.* ; Mayor, V.* ; McAteer, J.B.* ; Meyre, D.* ; Mitchell, B.D.* ; Mohlke, K.L.* ; Morken, M.A.* ; Narisu, N.* ; Palmer, C.N.A.* ; Pakyz, R.* ; Pascoe, L.* ; Payne, F.* ; Pearson, D.* ; Rathmann, W.* ; Sandbaek, A.* ; Sayer, A.A.* ; Scott, L.J.* ; Sharp, S.J.* ; Sijbrands, E.* ; Singleton, A.* ; Siscovick, D.S.* ; Smith, N.L.* ; Sparsø, T.* ; Swift, A.J.* ; Syddall, H.* ; Thorleifsson, G.* ; Tönjes, A.* ; Tuomi, T.* ; Tuomilehto, J.* ; Valle, T.T.* ; Waeber, G.* ; Walley, A.* ; Waterworth, D.M.* ; Zeggini, E.* ; Zhao, J.H.* ; Illig, T. ; Wichmann, H.-E. ; Wilson, J.F.* ; van Duijn, C.M.* ; Hu, F.B.* ; Morris, A.D.* ; Frayling, T.M.* ; Hattersley, A.T.* ; Thorsteinsdottir, U.* ; Stefansson, K.* ; Nilsson, P.* ; Syvanen, A.C.* ; Shuldiner, A.R.* ; Walker, M.* ; Bornstein, S.R.* ; Schwarz, P.* ; Williams, G.H.* ; Nathan, D.M.* ; Kuusisto, J.* ; Laakso, M.* ; Cooper, C.* ; Marmot, M.* ; Ferrucci, L.* ; Mooser, V.* ; Stumvoll, M.* ; Loos, R.J.F.* ; Altshuler, D.* ; Psaty, B.M.* ; Rotter, J.I.* ; Boerwinkle, E.* ; Hansen, T.* ; Pedersen, O.* ; Florez, J.C* ; McCarthy, M.I.* ; Boehnke, M.* ; Barroso, I.* ; Sladek, R.* ; Froguel, P.* ; Meigs, J.B.* ; Groop, L.* ; Wareham, N.J.* ; Watanabe, R.M.*

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

Nat. Genet. 42, 142-148 (2010)

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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)).

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