Variants in MTNR1B influence fasting glucose levels

Inga Prokopenko; Claudia Langenberg; Jose C. Florez; Richa Saxena; Nicole Soranzo; Gudmar Thorleifsson; Ruth J. F. Loos; Alisa K. Manning; Anne U. Jackson; Yurii Aulchenko; Simon C. Potter; Michael R. Erdos; Serena Sanna; Jouke-Jan Hottenga; Eleanor Wheeler; Marika Kaakinen; Valeriya Lyssenko; Wei-Min Chen; Kourosh 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 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 Orru; Colin N. A. Palmer; Anneli Pouta; Joshua Randall; Wolfgang Rathmann; Jouko Saramies; Paul Scheet; Laura J. Scott; Angelo Scuteri; Stephen Sharp; Eric Sijbrands; Jan H. Smit; Kijoung Song; Valgerdur Steinthorsdottir; Heather M. Stringham; Tiinamaija Tuomi; Jaakko Tuomilehto; Andre 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 Sandhu; Dorret I. Boomsma; Manuela Uda; Tim D. Spector; Brenda W. J. H. Penninx; David Altshuler; Peter Vollenweider; Marjo Riitta Jarvelin; Edward Lakatta; Gerard Waeber; Caroline S. Fox; Leena Peltonen; Leif C. Groop; Vincent Mooser; L. Adrienne Cupples; Unnur Thorsteinsdottir; Michael Boehnke; Ines Barroso

doi:10.1038/ng.290

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Variants in MTNR1B influence fasting glucose levels

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Variants in MTNR1B influence fasting glucose levels

Inga Prokopenko, Claudia Langenberg, Jose C. Florez, Richa Saxena, Nicole Soranzo, Gudmar Thorleifsson, Ruth J. F. Loos, Alisa K. Manning, Anne U. Jackson, Yurii Aulchenko, …

Nature genetics, Vol.41(1), pp.77-81

01/01/2009

DOI: https://doi.org/10.1038/ng.290

PMID: 19060907

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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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Title: Variants in MTNR1B influence fasting glucose levels
Creators: Inga Prokopenko - University of Oxford
Claudia Langenberg - Addenbrooke's Hospital
Jose C. Florez - Broad Institute
Richa Saxena - Broad Institute
Nicole Soranzo - Wellcome Sanger Institute
Gudmar Thorleifsson - deCODE Genet, IS-101 Reykjavik, Iceland
Ruth J. F. Loos - Addenbrooke's Hospital
Alisa K. Manning - Boston University
Anne U. Jackson - University of Michigan–Ann Arbor
Yurii Aulchenko - Erasmus University Rotterdam
Simon C. Potter - Wellcome Sanger Institute
Michael R. Erdos - National Human Genome Research Institute
Serena Sanna - Institute of Genetic and Biomedical Research
Jouke-Jan Hottenga - University of Amsterdam
Eleanor Wheeler - Wellcome Sanger Institute
Marika Kaakinen - University of Oulu
Valeriya Lyssenko - Lund University
Wei-Min Chen - University of Virginia
Kourosh Ahmadi - St Thomas' Hospital
Jacques S. Beckmann - University of Lausanne
Richard N. Bergman - University of Southern California
Murielle Bochud - University Hospital of Lausanne
Lori L. Bonnycastle - National Human Genome Research Institute
Thomas A. Buchanan - University of Southern California
Antonio Cao - Institute of Genetic and Biomedical Research
Alessandra Cervino - King's College London
Lachlan Coin - Imperial College London
Francis S. Collins - National Human Genome Research Institute
Laura Crisponi - Institute of Genetic and Biomedical Research
Eco J. C. De Geus - Vrije Universiteit Amsterdam
Abbas Dehghan - Erasmus University Rotterdam
Panos Deloukas - Wellcome Sanger Institute
Alex S. F. Doney - Ninewells Hospital
Paul Elliott - Imperial College London
Nelson Freimer - Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA
Vesela Gateva - University of Michigan–Ann Arbor
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Albert Hofman - Erasmus MC
Thomas E. Hughes - Novartis
Sarah Hunt - Wellcome Sanger Institute
Thomas Illig - Helmholtz Zentrum München
Michael Inouye - Wellcome Sanger Institute
Bo Isomaa - Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland
Toby Johnson - University of Lausanne
Augustine Kong - deCODE Genetics
Maria Krestyaninova - European Bioinformatics Institute
Johanna Kuusisto - Kuopio University Hospital
Markku Laakso - Kuopio University Hospital
Noha Lim - GlaxoSmithKline
Ulf Lindblad - Skaraborg Hospital
Cecilia M. Lindgren - University of Oxford
Owen T. McCann - Wellcome Sanger Institute
Karen L. Mohlke - University of North Carolina at Chapel Hill
Andrew D. Morris - Ninewells Hospital
Silvia Naitza - Institute of Genetic and Biomedical Research
Marco Orru - Institute of Genetic and Biomedical Research
Colin N. A. Palmer - University of Dundee
Anneli Pouta - Oulu University Hospital
Joshua Randall - Wellcome Centre for Human Genetics
Wolfgang Rathmann - Deutsches Diabetes-Zentrum e.V.
Jouko Saramies - Savitaipale Hlth Ctr, Savitaipale 54800, Finland
Paul Scheet - University of Michigan–Ann Arbor
Laura J. Scott - University of Michigan–Ann Arbor
Angelo Scuteri - National Human Genome Research Institute
Stephen Sharp - Medical Research Council
Eric Sijbrands - Erasmus MC
Jan H. Smit - University of Groningen
Kijoung Song - GlaxoSmithKline
Valgerdur Steinthorsdottir - deCODE Genet, IS-101 Reykjavik, Iceland
Heather M. Stringham - University of Michigan–Ann Arbor
Tiinamaija Tuomi - University of Helsinki
Jaakko Tuomilehto - University of Helsinki
Andre G. Uitterlinden - Erasmus MC
Benjamin F. Voight - Massachusetts General Hospital
Dawn Waterworth - GlaxoSmithKline
H-Erich Wichmann - Helmholtz Zentrum Muenchen, Natl Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany
Gonneke Willemsen - Vrije Universiteit Amsterdam
Jacqueline C. M. Witteman - Erasmus MC
Xin Yuan - New Frontier
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Eleftheria Zeggini - Wellcome Centre for Human Genetics
David Schlessinger - National Institute on Aging
Manjinder Sandhu - University of Cambridge
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Manuela Uda - Institute of Genetic and Biomedical Research
Tim D. Spector - King's College London
Brenda W. J. H. Penninx - University of Cambridge
David Altshuler - Massachusetts General Hospital
Peter Vollenweider - University Hospital of Lausanne
Marjo Riitta Jarvelin - University of Oulu
Edward Lakatta - National Institute on Aging
Gerard Waeber - University Hospital of Lausanne
Caroline S. Fox - Brigham and Women's Hospital
Leena Peltonen - Institute for Molecular Medicine Finland
Leif C. Groop - Lund University
Vincent Mooser - GlaxoSmithKline
L. Adrienne Cupples - Boston University
Unnur Thorsteinsdottir - University of Iceland
Michael Boehnke - University of Michigan–Ann Arbor
Ines Barroso - Wellcome Sanger Institute
Publication Details: Nature genetics, Vol.41(1), pp.77-81
Publisher: Springer Nature
Number of pages: 5
Date published: 01/01/2009
Grant note: G0601261 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) K24 DK080140-02; DK069922; R01 DK072193; DK-062370; R01 DK078616-01A1; DK-078616; R01 DK069922-02; R01 DK072193-04; U01 DK062370; U01 DK078616; K24 DK080140; R01 DK069922; R01 DK078616; R01 DK062370; K23 DK065978; R01 DK029867; DK-065978; R56 DK062370; R01 DK062370-05; K24 DK080140-01; DK-072193; K23 DK065978-05; DK-080140 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) N01HC25195; HC-25195; N01 HC025195; R01 HL087679-02; R01 HL087679; U01 HL084729; HL-087679; HL-084729; U01 HL084729-03; N02-HL-6-4278 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 089061; 076113; 077016; GR072960; 077011; 083948; 079557; 090532; GR069224 / Wellcome Trust; European Commission R01HL087679 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) DA-021519; U54 DA021519; U54 DA021519-04 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) MH059160; R01 MH059160-04 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) N01HC025195 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) ZIAAG000675 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01DK062370 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Identifiers: 99928743502346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Variants in MTNR1B influence fasting glucose levels

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