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Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Research Article
    • Abstract:
      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. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom
      2Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
      3Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      4King's College London, St. Thomas' Hospital Campus, London, United Kingdom
      5Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
      6Swiss Institute of Bioinformatics, Lausanne, Switzerland
      7William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
      8Institute for Maternal and Child Health—Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy
      9University of Trieste, Trieste, Italy
      10Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy
      11Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom
      12Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom
      13Estonian Genome Center, University of Tartu, Tartu, Estonia
      14Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland
      15Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
      16Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
      17Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America
      18Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands
      19Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
      20Institute of Genetics and Biophysics "A. Buzzati-Traverso"—Consiglio Nazionale delle Ricerche (CNR), Naples, Italy
      21Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
      22Icelandic Heart Association Research Institute, Kopavogur, Iceland
      23University of Iceland, Reykjavik, Iceland
      24Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0119752
    • Accession Number:
      101839201
  • Citations
    • ABNT:
      HUFFMAN, J. E. et al. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans. PLoS ONE, [s. l.], v. 10, n. 3, p. 1–21, 2015. DOI 10.1371/journal.pone.0119752. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=101839201&custid=s8280428. Acesso em: 10 ago. 2020.
    • AMA:
      Huffman JE, Albrecht E, Teumer A, et al. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans. PLoS ONE. 2015;10(3):1-21. doi:10.1371/journal.pone.0119752
    • APA:
      Huffman, J. E., Albrecht, E., Teumer, A., Mangino, M., Kapur, K., Johnson, T., Kutalik, Z., Pirastu, N., Pistis, G., Lopez, L. M., Haller, T., Salo, P., Goel, A., Li, M., Tanaka, T., Dehghan, A., Ruggiero, D., Malerba, G., Smith, A. V., & Nolte, I. M. (2015). Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans. PLoS ONE, 10(3), 1–21. https://doi.org/10.1371/journal.pone.0119752
    • Chicago/Turabian: Author-Date:
      Huffman, Jennifer E., Eva Albrecht, Alexander Teumer, Massimo Mangino, Karen Kapur, Toby Johnson, Zoltán Kutalik, et al. 2015. “Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans.” PLoS ONE 10 (3): 1–21. doi:10.1371/journal.pone.0119752.
    • Harvard:
      Huffman, J. E. et al. (2015) ‘Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans’, PLoS ONE, 10(3), pp. 1–21. doi: 10.1371/journal.pone.0119752.
    • Harvard: Australian:
      Huffman, JE, Albrecht, E, Teumer, A, Mangino, M, Kapur, K, Johnson, T, Kutalik, Z, Pirastu, N, Pistis, G, Lopez, LM, Haller, T, Salo, P, Goel, A, Li, M, Tanaka, T, Dehghan, A, Ruggiero, D, Malerba, G, Smith, AV & Nolte, IM 2015, ‘Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans’, PLoS ONE, vol. 10, no. 3, pp. 1–21, viewed 10 August 2020, .
    • MLA:
      Huffman, Jennifer E., et al. “Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans.” PLoS ONE, vol. 10, no. 3, Mar. 2015, pp. 1–21. EBSCOhost, doi:10.1371/journal.pone.0119752.
    • Chicago/Turabian: Humanities:
      Huffman, Jennifer E., Eva Albrecht, Alexander Teumer, Massimo Mangino, Karen Kapur, Toby Johnson, Zoltán Kutalik, et al. “Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans.” PLoS ONE 10, no. 3 (March 2015): 1–21. doi:10.1371/journal.pone.0119752.
    • Vancouver/ICMJE:
      Huffman JE, Albrecht E, Teumer A, Mangino M, Kapur K, Johnson T, et al. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans. PLoS ONE [Internet]. 2015 Mar [cited 2020 Aug 10];10(3):1–21. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=101839201&custid=s8280428