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Cited by 744

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Variants in MTNR1B influence fasting glucose levels

Open access
Prokopenko, Inga, Langenberg, Claudia, Florez, Jose C, Saxena, Richa, Soranzo, Nicole, Thorleifsson, Gudmar, Loos, Ruth J F, Manning, Alisa K, Jackson, Anne U, Aulchenko, Yurii, Potter, Simon C, Erdos, Michael R, Sanna, Serena, Hottenga, Jouke-Jan, Wheeler, Eleanor, Kaakinen, Marika, Lyssenko, Valeriya, Chen, Wei-Min, Ahmadi, Kourosh, Beckmann, Jacques S, Bergman, Richard N, Bochud, Murielle, Bonnycastle, Lori L, Buchanan, Thomas A, Cao, Antonio, Cervino, Alessandra, Coin, Lachlan, Collins, Francis S, Crisponi, Laura, de Geus, Eco J C, Dehghan, Abbas, Deloukas, Panos, Doney, Alex S F, Elliott, Paul, Freimer, Nelson, Gateva, Vesela, Herder, Christian, Hofman, Albert, Hughes, Thomas E, Hunt, Sarah, Illig, Thomas, Inouye, Michael, Isomaa, Bo, Johnson, Toby, Kong, Augustine, Krestyaninova, Maria, Kuusisto, Johanna, Laakso, Markku, Lim, Noha, Lindblad, Ulf, Lindgren, Cecilia M, McCann, Owen T, Mohlke, Karen L, Morris, Andrew D, Naitza, Silvia, Orrù, Marco, Palmer, Colin N A, Pouta, Anneli, Randall, Joshua, Rathmann, Wolfgang, Saramies, Jouko, Scheet, Paul, Scott, Laura J, Scuteri, Angelo, Sharp, Stephen, Sijbrands, Eric, Smit, Jan H, Song, Kijoung, Steinthorsdottir, Valgerdur, Stringham, Heather M, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Uitterlinden, André G, Voight, Benjamin F, Waterworth, Dawn, Wichmann, H-Erich, Willemsen, Gonneke, Witteman, Jacqueline C M, Yuan, Xin, Zhao, Jing Hua, Zeggini, Eleftheria, Schlessinger, David, Sandhu, Manjinder, Boomsma, Dorret I, Uda, Manuela, Spector, Tim D, Penninx, Brenda WJH, Altshuler, David, Vollenweider, Peter, Jarvelin, Marjo Riitta, Lakatta, Edward, Waeber, Gerard, Fox, Caroline S, Peltonen, Leena, Groop, Leif C, Mooser, Vincent, Cupples, L Adrienne, Thorsteinsdottir, Unnur, Boehnke, Michael, Barroso, Inês, Van Duijn, Cornelia, Dupuis, Josée, Watanabe, Richard M, Stefansson, Kari, McCarthy, Mark I, Wareham, Nicholas J, Meigs, James B, Abecasis, Gonçalo R·2009·Nature Genetics

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 × 10−50) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 × 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 × 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 × 10−57) and GCK (rs4607517, P = 1.0 × 10−25) loci.

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Authors
Prokopenko, I., Langenberg, C., Florez, J. C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R. J. F., Manning, A. K., Jackson, A. U., Aulchenko, Y., Potter, S. C., Erdos, M. R., Sanna, S., Hottenga, J.-J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., Beckmann, J. S., Bergman, R. N., Bochud, M., Bonnycastle, L. L., Buchanan, T. A., Cao, A., Cervino, A., Coin, L., Collins, F. S., Crisponi, L., de Geus, E. J. C., Dehghan, A., Deloukas, P., Doney, A. S. F., Elliott, P., Freimer, N., Gateva, V., Herder, C., Hofman, A., Hughes, T. E., Hunt, S., Illig, T., Inouye, M., Isomaa, B., Johnson, T., Kong, A., Krestyaninova, M., Kuusisto, J., Laakso, M., Lim, N., Lindblad, U., Lindgren, C. M., McCann, O. T., Mohlke, K. L., Morris, A. D., Naitza, S., Orrù, M., Palmer, C. N. A., Pouta, A., Randall, J., Rathmann, W., Saramies, J., Scheet, P., Scott, L. J., Scuteri, A., Sharp, S., Sijbrands, E., Smit, J. H., Song, K., Steinthorsdottir, V., Stringham, H. M., Tuomi, T., Tuomilehto, J., Uitterlinden, A. G., Voight, B. F., Waterworth, D., Wichmann, H.-E., Willemsen, G., Witteman, J. C. M., Yuan, X., Zhao, J. H., Zeggini, E., Schlessinger, D., Sandhu, M., Boomsma, D. I., Uda, M., Spector, T. D., Penninx, B. W., Altshuler, D., Vollenweider, P., Jarvelin, M. R., Lakatta, E., Waeber, G., Fox, C. S., Peltonen, L., Groop, L. C., Mooser, V., Cupples, L. A., Thorsteinsdottir, U., Boehnke, M., Barroso, I., Van Duijn, C., Dupuis, J., Watanabe, R. M., Stefansson, K., McCarthy, M. I., Wareham, N. J., Meigs, J. B., & Abecasis, G. R.
Venue
Nature Genetics
Published
2008-12-07
Volume
41
Issue
1
Pages
77-81
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2130259798
Cited by
744
References
31
FWCI
41.48
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Variants in MTNR1B influence fasting glucose levels. https://app.cochat.ai/papers/10.1038/ng.290
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Prokopenko, I., Langenberg, C., Florez, J. C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R. J. F., Manning, A. K., Jackson, A. U., Aulchenko, Y., Potter, S. C., Erdos, M. R., Sanna, S., Hottenga, J.-J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., . . . Abecasis, G. R. (2009). Variants in MTNR1B influence fasting glucose levels. Nature Genetics. https://doi.org/10.1038/ng.290

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