Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. (Articolo in rivista)

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  • Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Alternative label
  • Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, et al (2011)
    Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
    in Nature genetics (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, et al (literal)
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  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, UK 2Imperial College Healthcare National Health Service (NHS) Trust, London, UK 3Ealing Hospital NHS Trust, Middlesex, UK 4National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK 5Institute of Clinical Science, Imperial College London, Royal Brompton Hospital, London, UK 6Structural Bioinformatics Group, Division of Molecular Biosciences, Imperial College London, South Kensington, London, UK 7Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands 8deCODE genetics, Reykjavik, Iceland 9Istituto di Ricerca Genetica e Biomedica del Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy 10Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands 11Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Health Aging, Rotterdam, The Netherlands 12Institute for Community Medicine, University of Greifswald, Germany 13Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China 14Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 15Department of Neurology, Boston University School of Medicine, Boston Massachusetts, USA 16Department of Biological Psychology, VU University Amsterdam (VUA), Amsterdam, The Netherlands 17Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan 18Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 19Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK 20Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK 21Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA 22Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA 23Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge UK 24Institute of Social and Preventive Medicine (IUMSP), University Hospital and University of Lausanne, Lausanne, Switzerland 25Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK 26Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland 27Nuclear Magnetic Resonance (NMR) Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland 28Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA 29Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA 30Genetics, GlaxoSmithKline, King of Prussia, Pennsylvania, USA 31Boston University School of Medicine, Boston, Massachusetts, USA 32Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, USA 33The Diabetes Inflammation Laboratory, Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK 34Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand 35Neuroscience Campus Amsterdam, VUA and VUA Medical Center, Amsterdam, The Netherlands 36National Heart and Lung Institute, Imperial College London, London, UK 37Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 38Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 39IUMSP, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland 40Cardiology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland 41The Laboratory in Mjodd, Reykjavik, Iceland 42Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK 43Institute of Clinical Chemistry and Laboratory Medicine, University of Greifswald, Germany 44Genetics and Gastroenterology Divisions, Brigham and Women's Hospital, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA 45Harvard Medical School, Boston, Massachusetts, USA 46Harvard Stem Cell Institute, Cambridge, Massachusetts, USA 47Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, US National Institutes of Health (NIH), Bethesda, Maryland, USA 48Institute of Clinical Medicine, University of Oulu, Oulu, Finland 49CEA-IG Centre National de Genotypage, Evry Cedex, France 50Department of Medicine, University of Toronto, Toronto, Ontario, Canada 51Liver Center, Toronto Western Hospital, Toronto, Ontario, Canada 52Centre for Liver Research, University of Birmingham, Birmingham, UK 53Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany 54Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, UK 55Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands 56Clinical Pharmacology and The Genome Center, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK 57Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 58Institute of Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany 59Fondation Jean Dausset Ceph, Paris, France 60Department of Medicine A, University Medicine Greifswald, Greifswald, Germany 61Department of Genetics, Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA 62Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA 63Office of Biostatistics Research, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA 64Queensland Institute of Medical Research, Brisbane, Queensland, Australia 65Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA 66Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA 67Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA 68Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 69NHLBI Framingham Heart Study, Framingham, Massachusetts, USA 70Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland 71Department of Psychiatry and EMGO Institute for Health and Care Research, VUA Medical Centre, Amsterdam, The Netherlands 72Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands 73Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 74Department of Lifecourse and Services, National Institute for Health and Welfare, Oulu, Finland 75Institute of Diagnostics, Clinical Chemistry, University of Oulu, Oulu, Finland 76Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, University of Oulu, Oulu, Finland 77Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA 78Gesellschaft für Arterioskleroseforschung, Leibniz-Institut für Arterioskleroseforschung an der Universität Münster, Münster, Germany 79Department of Immunology, University of Toronto, Toronto, Ontario, Canada 80Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada 81Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada 82Toronto General Research Institute, Toronto, Ontario, Canada 83Department of Twin Research and Genetic Epidemiology, King's College London, London, UK 84Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA 85Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands 86Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 87LifeLines Cohort Study and Biobank, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 88Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA 89Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA 90Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany 91Klinikum Grosshadern, Munich, Germany 92EMGO+Institute, VUA Medical Center, Amsterdam, The Netherlands 93Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada 94Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA 96Center for Medical Systems Biology, Rotterdam, The Netherlands 97Genomics of Common Diseases, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK 98Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK 99Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 100Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Hospital, Helsinki, Finland 101The Institute for Molecular Medicine FIMM, Helsinki, Finland 102Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland 103MRC-Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College, London, UK 104Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 105Faculty of Medicine, Imperial College London, London, UK 106Faculty of Medicine, University of Iceland, Reykjavik, Iceland 107Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland 108Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital, Boston, Massachusetts, USA 109Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA 110Institute of Health Sciences, University of Oulu, Oulu, Finland 111Biocenter Oulu, University of Oulu, Oulu, Finland 112MRC-Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK (literal)
Titolo
  • Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. (literal)
Abstract
  • Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10-8 to P = 10-190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. (literal)
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