DOI: 10.1038/ng.290

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Variants in MTNR1B influence fasting glucose levels

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

Biology

Internal medicine

Endocrinology

2008

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.

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“Variants in MTNR1B influence fasting glucose levels” is a paper by Inga Prokopenko Claudia Langenberg José C. Florez Richa Saxena Nicole Soranzo Guðmar Þorleifsson Ruth J.F. Loos Alisa K. Manning Anne Jackson Yurii S. Aulchenko Simon Potter Michael R. Erdos Serena Sanna Jouke‐Jan Hottenga Eleanor Wheeler Marika Kaakinen Valeriya Lyssenko Weimin Chen Kourosh R. Ahmadi Jacques S. Beckmann Richard N. Bergman Murielle Bochud Lori L. Bonnycastle Thomas A. Buchanan Antonio Cao Alessandra Cervino Lachlan Coin Francis S. Collins Laura Crisponi Eco J. C. de Geus Abbas Dehghan Panos Deloukas Alex S.F. Doney Paul Elliott Nelson B. Freimer Vesela Gateva Christian Herder Albert Hofman Thomas E. Hughes Sarah Hunt Thomas Illig Michael Inouye Bo Isomaa Toby Johnson Augustine Kong Maria Krestyaninova Johanna Kuusisto Markku Laakso Noha Lim Ulf Lindblad Cecilia M. Lindgren Owen T. McCann Karen L. Mohlke Andrew D. Morris Silvia Naitza Marco Orrù Colin N.A. Palmer Anneli Pouta Joshua C. Randall Wolfgang Rathmann Jouko Saramies Paul Scheet Laura J. Scott Angelo Scuteri Stephen J. Sharp Eric J.G. Sijbrands Jan Smit Kijoung Song Valgerður Steinthórsdóttir Heather M. Stringham Tiinamaija Tuomi Jaakko Tuomilehto André G. Uitterlinden Benjamin F. Voight Dawn Waterworth H‐Erich Wichmann Gonneke Willemsen Jacqueline C. M. Witteman Xin Yuan Jing Hua Zhao Eleftheria Zeggini David Schlessinger Manjinder S. Sandhu Dorret I. Boomsma Manuela Uda Tim D. Spector Brenda W. J. H. Penninx David Altshuler Péter Vollenweider Marjo‐Riitta Järvelin Edward G. Lakatta Gérard Waeber Caroline S. Fox Leena Peltonen Leif Groop Vincent Mooser L. Adrienne Cupples Unnur Þorsteinsdóttir Michael Boehnke Inês Barroso Cornelia M. van Duijn Josée Dupuis Richard M. Watanabe Kári Stefánsson Mark I. McCarthy Nicholas J. Wareham James B. Meigs Gonçalo R. Abecasis published in 2008. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.