Back
Modulation of genetic associations with serum urate levels by body-mass-index in humans.
Journal article

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

  • Huffman JE Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Albrecht E Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Teumer A Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
  • Mangino M King's College London, St. Thomas' Hospital Campus, London, United Kingdom.
  • Kapur K Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Johnson T William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Kutalik Z Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Pirastu N Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
  • Pistis G Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
  • Lopez LM Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
  • Haller T Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Salo P Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland.
  • Goel A Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Li M Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Tanaka T Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America.
  • Dehghan A Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Ruggiero D Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
  • Malerba G Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
  • Smith AV Icelandic Heart Association Research Institute, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland.
  • Nolte IM Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Portas L Institute of Population Genetics, National Research Council of Italy, Sassari, Italy.
  • Phipps-Green A Department of Biochemistry, University of Otago, Dunedin, New Zealand.
  • Boteva L Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Navarro P Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Johansson A Uppsala Clinical Research Center, Uppsala University Hospital, Upsalla, Sweden; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
  • Hicks AA Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy; Affiliated Institute of the University of Lübeck, Lübeck, Germany.
  • Polasek O Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia.
  • Esko T Estonian Genome Center, University of Tartu, Tartu, Estonia; Broad Institute, Cambridge, MA, United States of America; Children's Hospital Boston, Boston, MA, United States of America.
  • Peden JF Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Harris SE Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom; Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom.
  • Murgia F Institute of Population Genetics, National Research Council of Italy, Sassari, Italy.
  • Wild SH Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Tenesa A Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom; Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom.
  • Tin A Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Mihailov E Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Grotevendt A Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
  • Gislason GK Icelandic Heart Association Research Institute, Kopavogur, Iceland.
  • Coresh J Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Welch Center for Prevention, Epidemiology and Clinical Research, John Hopkins University, Baltimore, MD, United States of America.
  • D'Adamo P Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
  • Ulivi S Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy.
  • Vollenweider P Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Waeber G Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Campbell S Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Kolcic I Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia.
  • Fisher K Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Viigimaa M Tallinn University of Technology, Department of Biomedical Engineering, Chair of Medical Physics, Tallinn, Estonia; Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia.
  • Metter JE Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America.
  • Masciullo C Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
  • Trabetti E Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
  • Bombieri C Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
  • Sorice R Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
  • Döring A Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Reischl E Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Strauch K Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany.
  • Hofman A Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Uitterlinden AG Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Waldenberger M Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Wichmann HE Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany; Klinikum Grosshadern, Munich, Germany.
  • Davies G Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
  • Gow AJ Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
  • Dalbeth N Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
  • Stamp L Department of Medicine, University of Otago, Christchurch, New Zealand.
  • Smit JH Department of Psychiatry/EMGO Institute, VU University Medical Centre, Amsterdam, the Netherlands.
  • Kirin M Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Nagaraja R Laboratory of Genetics, National Institute on Aging (NIA), Baltimore, MD, United States of America.
  • Nauck M Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
  • Schurmann C Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
  • Budde K Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
  • Farrington SM Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Theodoratou E Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Jula A Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland.
  • Salomaa V Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland.
  • Sala C Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
  • Hengstenberg C University Hospital Regensburg, Regensburg, Germany.
  • Burnier M Department of Medicine, Nephrology Division, Lausanne University Hospital, Lausanne, Switzerland.
  • Mägi R Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Klopp N Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany.
  • Kloiber S Max Planck Institute of Psychiatry, Munich, Germany.
  • Schipf S Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Ripatti S Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland; Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland.
  • Cabras S Department of Mathematics and Informatics, Università di Cagliari, Cagliari, Italy; Department of Statistics, Universidad Carlos III de Madrid, Madrid, Spain.
  • Soranzo N Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
  • Homuth G Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
  • Nutile T Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
  • Munroe PB William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Hastie N Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Campbell H Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Rudan I Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia; Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Cabrera C Queen Mary, University of London, London, United Kingdom.
  • Haley C Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom; Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom.
  • Franco OH Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Merriman TR Department of Biochemistry, University of Otago, Dunedin, New Zealand.
  • Gudnason V Icelandic Heart Association Research Institute, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland.
  • Pirastu M Institute of Population Genetics, National Research Council of Italy, Sassari, Italy.
  • Penninx BW Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Snieder H Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Metspalu A Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Ciullo M Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
  • Pramstaller PP Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy; Affiliated Institute of the University of Lübeck, Lübeck, Germany.
  • van Duijn CM Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Ferrucci L Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America.
  • Gambaro G Institute of Internal Medicine, Renal Program, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy.
  • Deary IJ Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
  • Dunlop MG Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Wilson JF Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • Gasparini P Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
  • Gyllensten U Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
  • Spector TD King's College London, St. Thomas' Hospital Campus, London, United Kingdom.
  • Wright AF Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Hayward C Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
  • Watkins H on behalf of PROCARDIS; Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Perola M Estonian Genome Center, University of Tartu, Tartu, Estonia; Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland.
  • Bochud M University Institute of Social and Preventive Medicine, Lausanne, Switzerland.
  • Kao WH Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Welch Center for Prevention, Epidemiology and Clinical Research, John Hopkins University, Baltimore, MD, United States of America.
  • Caulfield M William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Toniolo D Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
  • Völzke H Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Gieger C Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Köttgen A Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Renal Division, Freiburg University Hospital, Freiburg, Germany.
  • Vitart V Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom.
Show more…
  • 2015-03-27
Published in:
  • PloS one. - 2015
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Antigens, Nuclear
Body Mass Index
Edar Receptor
Female
Genetic Loci
Genome-Wide Association Study
Genotype
Gout
Humans
Linear Models
Male
Membrane Glycoproteins
Neoplasm Proteins
Nerve Tissue Proteins
Obesity
Overweight
Oxidoreductases Acting on Sulfur Group Donors
Polymorphism, Single Nucleotide
Risk Factors
Uric Acid
English We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/20374
Statistics
Document views: 20 File downloads: