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Variants in MTNR1B influence fasting glucose levels

Prokopenko, Inga; Langenberg, Claudia; Florez, Jose C.; Saxena, Richa; Soranzo, Nicole; Thorleifsson, Gudmar; Loos, Ruth J. F.; Manning, Alisa K.; Jackson, Anne U. and Aulchenko, Yurii, et al. (2009) In Nature Genetics 41(1). p.77-81
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... (More)
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. (Less)
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Nature Genetics
volume
41
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1
pages
77 - 81
publisher
Nature Publishing Group
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  • wos:000262085300019
  • scopus:58149156287
ISSN
1546-1718
DOI
10.1038/ng.290
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English
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99652da4-3dd8-4107-adfe-b3a1f6f5d607 (old id 1313201)
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@article{99652da4-3dd8-4107-adfe-b3a1f6f5d607,
  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.},
  author       = {Prokopenko, Inga and Langenberg, Claudia and Florez, Jose C. and Saxena, Richa and Soranzo, Nicole and Thorleifsson, Gudmar and Loos, Ruth J. F. and Manning, Alisa K. and Jackson, Anne U. and Aulchenko, Yurii and Potter, Simon C. and Erdos, Michael R. and Sanna, Serena and Hottenga, Jouke-Jan and Wheeler, Eleanor and Kaakinen, Marika and Lyssenko, Valeriya and Chen, Wei-Min and Ahmadi, Kourosh and Beckmann, Jacques S. and Bergman, Richard N. and Bochud, Murielle and Bonnycastle, Lori L. and Buchanan, Thomas A. and Cao, Antonio and Cervino, Alessandra and Coin, Lachlan and Collins, Francis S. and Crisponi, Laura and De Geus, Eco J. C. and Dehghan, Abbas and Deloukas, Panos and Doney, Alex S. F. and Elliott, Paul and Freimer, Nelson and Gateva, Vesela and Herder, Christian and Hofman, Albert and Hughes, Thomas E. and Hunt, Sarah and Illig, Thomas and Inouye, Michael and Isomaa, Bo and Johnson, Toby and Kong, Augustine and Krestyaninova, Maria and Kuusisto, Johanna and Laakso, Markku and Lim, Noha and Lindblad, Ulf and Lindgren, Cecilia M. and McCann, Owen T. and Mohlke, Karen L. and Morris, Andrew D. and Naitza, Silvia and Orru, Marco and Palmer, Colin N. A. and Pouta, Anneli and Randall, Joshua and Rathmann, Wolfgang and Saramies, Jouko and Scheet, Paul and Scott, Laura J. and Scuteri, Angelo and Sharp, Stephen and Sijbrands, Eric and Smit, Jan H. and Song, Kijoung and Steinthorsdottir, Valgerdur and Stringham, Heather M. and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Uitterlinden, Andre G. and Voight, Benjamin F. and Waterworth, Dawn and Wichmann, H-Erich and Willemsen, Gonneke and Witteman, Jacqueline C. M. and Yuan, Xin and Zhao, Jing Hua and Zeggini, Eleftheria and Schlessinger, David and Sandhu, Manjinder and Boomsma, Dorret I. and Uda, Manuela and Spector, Tim D. and Penninx, Brenda W. J. H. and Altshuler, David and Vollenweider, Peter and Jarvelin, Marjo Riitta and Lakatta, Edward and Waeber, Gerard and Fox, Caroline S. and Peltonen, Leena and Groop, Leif and Mooser, Vincent and Cupples, L. Adrienne and Thorsteinsdottir, Unnur and Boehnke, Michael and Barroso, Ines and Van Duijn, Cornelia and Dupuis, Josee and Watanabe, Richard M. and Stefansson, Kari and McCarthy, Mark I. and Wareham, Nicholas J. and Meigs, James B. and Abecasis, Goncalo R.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {1},
  pages        = {77--81},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Variants in MTNR1B influence fasting glucose levels},
  url          = {http://dx.doi.org/10.1038/ng.290},
  volume       = {41},
  year         = {2009},
}