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; Cornelia Van Duijn; Josee Dupuis; Richard M. Watanabe; Kari Stefansson; Mark I. McCarthy; Nicholas J. Wareham; James B. Meigs; Goncalo R. Abecasis; Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa

doi:10.1038/ng.290

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Variants in MTNR1B influence fasting glucose levels

Journal article

Peer reviewed

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 - without role: Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Claudia Langenberg - Addenbrooke's Hospital
Jose C. Florez - Massachusetts General Hospital
Richa Saxena - Center for Human Genetics
Nicole Soranzo - Wellcome Sanger Institute
Gudmar Thorleifsson - deCODE Genetics
Ruth J. F. Loos - Addenbrooke's Hospital
Alisa K. Manning - Boston University
Anne U. Jackson - University of Michigan–Ann Arbor
Yurii Aulchenko - Erasmus MC
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 - Vrije Universiteit Amsterdam
Eleanor Wheeler - Wellcome Sanger Institute
Marika Kaakinen - University of Oulu
Valeriya Lyssenko - Lund University
Wei-Min Chen - University of Virginia
Kourosh Ahmadi - King's College London
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 - St Thomas' Hospital
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 - Neurobehavioral Research
Vesela Gateva - University of Michigan–Ann Arbor
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Albert Hofman - Erasmus MC
Thomas E. Hughes - Novartis Inst BioMed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA
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 - New Frontier
Ulf Lindblad - Malmö University
Cecilia M. Lindgren - Wellcome Centre for Human Genetics
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 - Ninewells Hospital
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 - Addenbrooke's Hospital
Eric Sijbrands - Erasmus MC
Jan H. Smit - University Medical Center Groningen
Kijoung Song - New Frontier
Valgerdur Steinthorsdottir - deCODE Genetics
Heather M. Stringham - University of Michigan–Ann Arbor
Tiinamaija Tuomi - University of Helsinki
Jaakko Tuomilehto - Northern Ostrobothnia Hospital District
Andre G. Uitterlinden - Erasmus MC
Benjamin F. Voight - Center for Human Genetics
Dawn Waterworth - GlaxoSmithKline
H-Erich Wichmann - Ludwig-Maximilians-Universität München
Gonneke Willemsen - Vrije Universiteit Amsterdam
Jacqueline C. M. Witteman - Erasmus University Rotterdam
Xin Yuan - GlaxoSmithKline
Jing Hua Zhao - Addenbrooke's Hospital
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 - Leiden University Medical Center
David Altshuler - Center for Human Genetics
Peter Vollenweider - University Hospital of Lausanne
Marjo Riitta Jarvelin - Imperial College London
Edward Lakatta - National Institute on Aging
Gerard Waeber - University Hospital of Lausanne
Caroline S. Fox - Framingham Heart Study
Leena Peltonen - Wellcome Sanger Institute
Leif C. Groop - Malmö University
Vincent Mooser - New Frontier
L. Adrienne Cupples - Boston University
Unnur Thorsteinsdottir - University of Iceland
Michael Boehnke - University of Michigan–Ann Arbor
Ines Barroso - Wellcome Sanger Institute
Cornelia Van Duijn - Erasmus MC
Josee Dupuis - Boston University
Richard M. Watanabe - Supreme Council Of Health
Kari Stefansson - deCODE Genet, IS-101 Reykjavik, Iceland
Mark I. McCarthy - University of Oxford
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
James B. Meigs - Harvard University
Goncalo R. Abecasis - Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa
Publication Details: Nature genetics, Vol.41(1), pp.77-81
Publisher: Springer Nature
Number of pages: 5
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) G0000649; G0701863; G0601261; G0500539; G016121; MC_U106188470; MC_U106179471 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R01MH059160 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) U54DA021519 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission Z01 HG000024 / Intramural NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA RR-163736 / NCRR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) ZIAHG000024 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01 HG002651-05; R01 HG002651; HG-02651 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Identifiers: 9939550308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article