Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways. (Articolo in rivista)

Type
Label
  • Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.2337/db10-0502 (literal)
Alternative label
  • Nicole Soranzo;1,2 Serena Sanna;3 Eleanor Wheeler;1 Christian Gieger;4 Dörte Radke;5 Josée Dupuis;6,7 Nabila Bouatia-Naji;8 Claudia Langenberg;9 Inga Prokopenko;10,11 Elliot Stolerman;12,13,14 Manjinder S. Sandhu;9,15,16 Matthew M. Heeney;17 Joseph M. Devaney;18 Muredach P. Reilly;19,20 Sally L. Ricketts;15 Alexandre F.R. Stewart;21 Benjamin F. Voight;12,13,22 Christina Willenborg;23,24 Benjamin Wright;25 David Altshuler;12,13,14 Dan Arking;26 Beverley Balkau;27,28 Daniel Barnes;9 Eric Boerwinkle;29 Bernhard Böhm;30 Amélie Bonnefond;8 Lori L. Bonnycastle;31 Dorret I. Boomsma;32 Stefan R. Bornstein;33 Yvonne Böttcher;34 Suzannah Bumpstead;1 Mary Susan Burnett-Miller;18 Harry Campbell;35 Antonio Cao;3 John Chambers;36 Robert Clark;37 Francis S. Collins;31 Josef Coresh;38 Eco J.C. de Geus;32 Mariano Dei;3 Panos Deloukas;1 Angela Döring;4 Josephine M. Egan;39 Roberto Elosua;40 Luigi Ferrucci;41 Nita Forouhi;9 Caroline S. Fox;7,42 Christopher Franklin;35 Maria Grazia Franzosi;43 Sophie Gallina;8 Anuj Goel;11,44 Jürgen Graessler;33 Harald Grallert;4 Andreas Greinacher;45 David Hadley;46 Alistair Hall;47 Anders Hamsten on behalf of Procardis Consortium;48 Caroline Hayward;49 Simon Heath;50 Christian Herder;51 Georg Homuth;52 Jouke-Jan Hottenga;32 Rachel Hunter-Merrill;6 Thomas Illig;4 Anne U. Jackson;53 Antti Jula;54 Marcus Kleber;55 Christopher W. Knouff;56 Augustine Kong;57 Jaspal Kooner;58 Anna Köttgen;59 Peter Kovacs;60 Knut Krohn;60 Brigitte Kühnel;4 Johanna Kuusisto;61 Markku Laakso;61 Mark Lathrop;62 Cécile Lecoeur;8 Man Li;59 Mingyao Li;63 Ruth J.F. Loos;9 Jian'an Luan;9 Valeriya Lyssenko;64 Reedik Mägi;10,11 Patrik K.E. Magnusson;65 Anders Mälarstig;48 Massimo Mangino;2 María Teresa Martínez-Larrad;66,67 Winfried März;55 Wendy L. McArdle;68 Ruth McPherson;21 Christa Meisinger;4 Thomas Meitinger;69,70 Olle Melander;64 Karen L. Mohlke;71 Vincent E. Mooser;56 Mario A. Morken;31 Narisu Narisu;31 David M. Nathan;14,72 Matthias Nauck;73 Chris O'Donnell;7 Konrad Oexle;69 Nazario Olla;3 James S. Pankow;74 Felicity Payne;1 John F. Peden;11,44 Nancy L. Pedersen;65 Leena Peltonen;1,75,76 Markus Perola;76,77 Ozren Polasek;78,79 Eleonora Porcu;3 Daniel J. Rader;19,20 Wolfgang Rathmann;80 Samuli Ripatti;76,77 Ghislain Rocheleau;81,82 Michael Roden;51,83 Igor Rudan;35,84 Veikko Salomaa;77 Richa Saxena;12,13 David Schlessinger;85 Heribert Schunkert;24 Peter Schwarz;33 Udo Seedorf;86 Elizabeth Selvin;38 Manuel Serrano-Ríos;66,67 Peter Shrader;87 Angela Silveira;48 David Siscovick;88 Kjioung Song;56 Timothy D. Spector;2 Kari Stefansson;89,90 Valgerdur Steinthorsdottir;89 David P. Strachan;46 Rona Strawbridge;48 Michael Stumvoll;34,91 Ida Surakka;76,77 Amy J. Swift;31 Toshiko Tanaka;41,92 Alexander Teumer;52 Gudmar Thorleifsson;57 Unnur Thorsteinsdottir;89,90 Anke Tönjes;34 Gianluca Usala;3 Veronique Vitart;49 Henry Völzke;5 Henri Wallaschofski;73 Dawn M. Waterworth;56 Hugh Watkins;11,44 H-Erich Wichmann;4,93,94 Sarah H. Wild;35 Gonneke Willemsen;32 Gordon H. Williams;14,42 James F. Wilson;35 Juliane Winkelmann;69,70,95 Alan F. Wright;49 WTCCC;96 Carina Zabena;66,67 Jing Hua Zhao;9 Stephen E. Epstein;18 Jeanette Erdmann;24 Hakon H. Hakonarson;97 Sekar Kathiresan;12,13,14,98 Kay-Tee Khaw;99 Robert Roberts;21 Nilesh J. Samani;47 Mark D. Fleming;100 Robert Sladek;81,82 Gonçalo Abecasis;53 Michael Boehnke;53 Philippe Froguel;8,101 Leif Groop;64 Mark I. McCarthy;10,11,102 W.H. Linda Kao;103 Jose C. Florez;12,13,14,72 Manuela Uda;3 Nicholas J. Wareham;9 Inês Barroso;1 and James B. Meigs14,87 (2010)
    Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways.
    in Diabetes (N.Y.N.Y.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Nicole Soranzo;1,2 Serena Sanna;3 Eleanor Wheeler;1 Christian Gieger;4 Dörte Radke;5 Josée Dupuis;6,7 Nabila Bouatia-Naji;8 Claudia Langenberg;9 Inga Prokopenko;10,11 Elliot Stolerman;12,13,14 Manjinder S. Sandhu;9,15,16 Matthew M. Heeney;17 Joseph M. Devaney;18 Muredach P. Reilly;19,20 Sally L. Ricketts;15 Alexandre F.R. Stewart;21 Benjamin F. Voight;12,13,22 Christina Willenborg;23,24 Benjamin Wright;25 David Altshuler;12,13,14 Dan Arking;26 Beverley Balkau;27,28 Daniel Barnes;9 Eric Boerwinkle;29 Bernhard Böhm;30 Amélie Bonnefond;8 Lori L. Bonnycastle;31 Dorret I. Boomsma;32 Stefan R. Bornstein;33 Yvonne Böttcher;34 Suzannah Bumpstead;1 Mary Susan Burnett-Miller;18 Harry Campbell;35 Antonio Cao;3 John Chambers;36 Robert Clark;37 Francis S. Collins;31 Josef Coresh;38 Eco J.C. de Geus;32 Mariano Dei;3 Panos Deloukas;1 Angela Döring;4 Josephine M. Egan;39 Roberto Elosua;40 Luigi Ferrucci;41 Nita Forouhi;9 Caroline S. Fox;7,42 Christopher Franklin;35 Maria Grazia Franzosi;43 Sophie Gallina;8 Anuj Goel;11,44 Jürgen Graessler;33 Harald Grallert;4 Andreas Greinacher;45 David Hadley;46 Alistair Hall;47 Anders Hamsten on behalf of Procardis Consortium;48 Caroline Hayward;49 Simon Heath;50 Christian Herder;51 Georg Homuth;52 Jouke-Jan Hottenga;32 Rachel Hunter-Merrill;6 Thomas Illig;4 Anne U. Jackson;53 Antti Jula;54 Marcus Kleber;55 Christopher W. Knouff;56 Augustine Kong;57 Jaspal Kooner;58 Anna Köttgen;59 Peter Kovacs;60 Knut Krohn;60 Brigitte Kühnel;4 Johanna Kuusisto;61 Markku Laakso;61 Mark Lathrop;62 Cécile Lecoeur;8 Man Li;59 Mingyao Li;63 Ruth J.F. Loos;9 Jian'an Luan;9 Valeriya Lyssenko;64 Reedik Mägi;10,11 Patrik K.E. Magnusson;65 Anders Mälarstig;48 Massimo Mangino;2 María Teresa Martínez-Larrad;66,67 Winfried März;55 Wendy L. McArdle;68 Ruth McPherson;21 Christa Meisinger;4 Thomas Meitinger;69,70 Olle Melander;64 Karen L. Mohlke;71 Vincent E. Mooser;56 Mario A. Morken;31 Narisu Narisu;31 David M. Nathan;14,72 Matthias Nauck;73 Chris O'Donnell;7 Konrad Oexle;69 Nazario Olla;3 James S. Pankow;74 Felicity Payne;1 John F. Peden;11,44 Nancy L. Pedersen;65 Leena Peltonen;1,75,76 Markus Perola;76,77 Ozren Polasek;78,79 Eleonora Porcu;3 Daniel J. Rader;19,20 Wolfgang Rathmann;80 Samuli Ripatti;76,77 Ghislain Rocheleau;81,82 Michael Roden;51,83 Igor Rudan;35,84 Veikko Salomaa;77 Richa Saxena;12,13 David Schlessinger;85 Heribert Schunkert;24 Peter Schwarz;33 Udo Seedorf;86 Elizabeth Selvin;38 Manuel Serrano-Ríos;66,67 Peter Shrader;87 Angela Silveira;48 David Siscovick;88 Kjioung Song;56 Timothy D. Spector;2 Kari Stefansson;89,90 Valgerdur Steinthorsdottir;89 David P. Strachan;46 Rona Strawbridge;48 Michael Stumvoll;34,91 Ida Surakka;76,77 Amy J. Swift;31 Toshiko Tanaka;41,92 Alexander Teumer;52 Gudmar Thorleifsson;57 Unnur Thorsteinsdottir;89,90 Anke Tönjes;34 Gianluca Usala;3 Veronique Vitart;49 Henry Völzke;5 Henri Wallaschofski;73 Dawn M. Waterworth;56 Hugh Watkins;11,44 H-Erich Wichmann;4,93,94 Sarah H. Wild;35 Gonneke Willemsen;32 Gordon H. Williams;14,42 James F. Wilson;35 Juliane Winkelmann;69,70,95 Alan F. Wright;49 WTCCC;96 Carina Zabena;66,67 Jing Hua Zhao;9 Stephen E. Epstein;18 Jeanette Erdmann;24 Hakon H. Hakonarson;97 Sekar Kathiresan;12,13,14,98 Kay-Tee Khaw;99 Robert Roberts;21 Nilesh J. Samani;47 Mark D. Fleming;100 Robert Sladek;81,82 Gonçalo Abecasis;53 Michael Boehnke;53 Philippe Froguel;8,101 Leif Groop;64 Mark I. McCarthy;10,11,102 W.H. Linda Kao;103 Jose C. Florez;12,13,14,72 Manuela Uda;3 Nicholas J. Wareham;9 Inês Barroso;1 and James B. Meigs14,87 (literal)
Pagina inizio
  • 3229 (literal)
Pagina fine
  • 3239 (literal)
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  • 59 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 12 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1Human Genetics, Wellcome Trust Sanger Institute, Hinxton, U.K.; the 2Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.; 3Istituto di Neurogenetica e Neurofarmacologia, CNR, Monserrato, Italy; the 4Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; the 5Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany; the 6Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; the 7National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; 8CNRS-UMR-8090, Institut Pasteur de Lille and Lille 2 University, Lille, France; the 9MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K.; the 10Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.; the 11Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.; the 12Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; the 13Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts; the 14Department of Medicine, Harvard Medical School, Boston, Massachusetts; the 15Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, U.K.; the 16Wellcome Trust Sanger Institute, Hinxton, Cambridge, U.K.; the 17Hematology Division, Children's Hospital Boston, Boston, Massachusetts; the 18Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, D.C.; the 19Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; the 20Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania; 21Medicine, University of Ottawa Heart Institute, Ottawa, Canada; the 22Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts; 23Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany; 24Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany; the 25Department of Health Sciences, University of Leicester, Leicester, U.K.; the 26McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Johns Hopkins University, Baltimore, Maryland; 27INSERM U70, Villejuif, France; 28University Paris-Sud, Orsay, France; the 29Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas; the 30Division of Endocrinology and Diabetes, Graduate School Molecular Endocrinology and Diabetes, University of Ulm, Ulm, Germany; the 31Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland; 32Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands; the 33Department of Medicine III, Division Prevention and Care of Diabetes, University of Dresden, Dresden, Germany; the 34Department of Medicine, University of Leipzig, Leipzig, Germany; the 35Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland; the 36Department of Epidemiology and Public Health, Imperial College London, London, U.K.; the 37Clinical Trials Services Unit, University of Oxford, Oxford, U.K.; the 38Departments of Epidemiology, Biostatistics, and Medicine, Johns Hopkins University, Baltimore, Maryland; the 39Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland; 40Cardiovascular Epidemiology and Genetics, Institut Municipal D'investigacio Medica, and CIBER Epidemiología y Salud Publica, Barcelona, Spain; the 41Clinical Research Branch, National Institute on Aging, Baltimore, Maryland; the 42Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts; 43Dipartimento di Ricerca Cardiovascolare, Istituto di Ricerche Farmacologiche \"Mario Negri,\" Milano, Italy; the 44Department of Cardiovascular Medicine, University of Oxford, Oxford, U.K.; 45Immunology and Transfusion Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany; the 46Division of Community Health Sciences, St George's, University of London, London, U.K.; 47Cardiovascular Sciences, University of Leicester, Leicester, U.K.; the 48Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; the 49Human Genetics Unit, Medical Research Council, Edinburgh, U.K.; 50Statistical Genetics, Centre National de Genotypage, Evry, France; the 51Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; the 52Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University Greifswald, Greifswald, Germany; the 53Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan; 54Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland; 55LURIC Study nonprofit LLC, Freiburg, Germany; 56Genetics, Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania; 57Statistics, deCODE genetics, Reykjavik, Iceland; the 58National Heart and Lung Institute, Hammersmith Hospital Campus, Imperial College London, London, U.K.; the 59Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland; the 60Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany; the 61Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland; 62Centre National de Genotypage, Evry, France; 63Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; the 64Department of Clinical Sciences, Lund University, Malmö, Sweden; the 65Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; the 66Diabetes and Lipids Research Laboratory, Madrid, Spain; 67Fundación Investigación Biomédica del Hospital Clínico San Carlos, Madrid, Spain; the 68Department of Social Medicine, University of Bristol, Bristol, U.K.; the 69Institute of Human Genetics, Technische Universität München, München, Germany; the 70Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; the 71Department of Genetics, University of North Carolina, Chapel Hill, North Carolina; the 72Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital, Boston, Massachusetts; the 73Institute for Clinical Chemistry and Laboratory Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany; the 74Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota; the 75Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; 76The Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland; 77Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; 78Andrija Stampar School of Public Health, University of Zagreb Medical School, Zagreb, Croatia; 79Gen-Info Ltd., Zagreb, Croatia; the 80Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; the 81Department of Human Genetics, Faculty of Medicine, McGill University Montreal, Montreal, Canada; the 82Genome Quebec Innovation Centre, Montreal, Canada; the 83Department of Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; the 84Croatian Centre for Global Health, University of Split Medical School, Split, Croatia; the 85Gerontology Research Center, National Institute on Aging, Baltimore, Maryland; 86Leibniz-Institut für Arterioskleroseforschung an der Universität Münster, Universität Münster, Münster, Germany; the 87General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts; the 88Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington; 89Population Genomics, deCODE genetics, Reykjavik, Iceland; the 90Faculty of Medicine, University of Iceland, Reykjavik, Iceland; the 91LIFE Study Centre, University of Leipzig, Leipzig, Germany; the 92MedStar Research Institute, Baltimore, Maryland; the 93Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany; 94Klinikum Grosshadern, Munich, Germany; the 95Department of Neurology, Technische Universität München, München, Germany; the 96Wellcome Trust Case Control Consortium; the 97Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; the 98Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; 99Public Health and Primary Care, Clinical Gerontology Unit, University of Cambridge, Cambridge, U.K.; the 100Pathology Division, Children's Hospital Boston, Boston, Massachusetts; 101Genomic Medicine, Hammersmith Hospital, Imperial College London, London, U.K.; 102Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, U.K.; and 103Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland. (literal)
Titolo
  • Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways. (literal)
Abstract
  • OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10-26), HFE (rs1800562/P = 2.6 × 10-20), TMPRSS6 (rs855791/P = 2.7 × 10-14), ANK1 (rs4737009/P = 6.1 × 10-12), SPTA1 (rs2779116/P = 2.8 × 10-9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10-9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10-54), MTNR1B (rs1387153/P = 4.0 × 10-11), GCK (rs1799884/P = 1.5 × 10-20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10-18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ~2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c. (literal)
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