Variants in MTNR1B influence fasting glucose levels

I Prokopenko, C Langenberg, JC Florez, R Saxena, N Soranzo, G Thorleifsson, RJF Loos, AK Manning, AU Jackson, Yuriy Aulchenko, SC Potter, MR Erdos, S Sanna, JJ (Jouke Jan) Hottenga, E Wheeler, M Kaakinen, V Lyssenko, WM Chen, K Ahmadi, JS BeckmannRN Bergman, M Bochud, LL Bonnycastle, TA Buchanan, A Cao, A Cervino, L Coin, FS Collins, L Crisponi, EJC de Geus, Abbas Dehghan, P Deloukas, ASF Doney, P Elliott, N Freimer, V Gateva, Cindy Herder, Bert Hofman, TE Hughes, S Hunt, T Illig, M Inouye, B Isomaa, T Johnson, A Kong, M Krestyaninova, J Kuusisto, M Laakso, N Lim, U Lindblad, CM Lindgren, OT McCann, KL Mohlke, AD Morris, S Naitza, M Orru, CNA Palmer, A Pouta, J Randall, W Rathmann, J Saramies, P Scheet, LJ Scott, A Scuteri, S Sharp, E.J.G. Sijbrands, JH Smit, K Song, V Steinthorsdottir, HM Stringham, T Tuomi, J Tuomilehto, André Uitterlinden, BF Voight, D Waterworth, HE Wichmann, G Willemsen, JCM Witteman, X Yuan, JH Zhao, E Zeggini, D Schlessinger, M Sandhu, DI Boomsma, M Uda, TD Spector, BWJH Penninx, D Altshuler, P Vollenweider, MR Jarvelin, E Lakatta, G Waeber, CS Fox, L Peltonen, LC Groop, V Mooser, LA Cupples, U Thorsteinsdottir, M Boehnke

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Abstract

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
Original languageUndefined/Unknown
Pages (from-to)77-81
Number of pages5
JournalNature Genetics
Volume41
Issue number1
DOIs
Publication statusPublished - 2009

Research programs

  • EMC COEUR-09
  • EMC MM-01-39-02
  • EMC NIHES-01-64-01

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