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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus.
Tin, Adrienne; Schlosser, Pascal; Matias-Garcia, Pamela R; Thio, Chris H L; Joehanes, Roby; Liu, Hongbo; Yu, Zhi; Weihs, Antoine; Hoppmann, Anselm; Grundner-Culemann, Franziska; Min, Josine L; Kuhns, Victoria L Halperin; Adeyemo, Adebowale A; Agyemang, Charles; Ärnlöv, Johan; Aziz, Nasir A; Baccarelli, Andrea; Bochud, Murielle; Brenner, Hermann; Bressler, Jan; Breteler, Monique M B; Carmeli, Cristian; Chaker, Layal; Coresh, Josef; Corre, Tanguy; Correa, Adolfo; Cox, Simon R; Delgado, Graciela E; Eckardt, Kai-Uwe; Ekici, Arif B; Endlich, Karlhans; Floyd, James S; Fraszczyk, Eliza; Gao, Xu; Gào, Xin; Gelber, Allan C; Ghanbari, Mohsen; Ghasemi, Sahar; Gieger, Christian; Greenland, Philip; Grove, Megan L; Harris, Sarah E; Hemani, Gibran; Henneman, Peter; Herder, Christian; Horvath, Steve; Hou, Lifang; Hurme, Mikko A; Hwang, Shih-Jen; Kardia, Sharon L R.
Afiliação
  • Tin A; Department of Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA. atin@umc.edu.
  • Schlosser P; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. atin@umc.edu.
  • Matias-Garcia PR; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Thio CHL; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
  • Joehanes R; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.
  • Liu H; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.
  • Yu Z; TUM School of Medicine, Technical University of Munich, Munich, Germany.
  • Weihs A; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Hoppmann A; Framingham Heart Study, Framingham, MA, USA.
  • Grundner-Culemann F; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Min JL; Department of Medicine and Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, PA, USA.
  • Kuhns VLH; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Adeyemo AA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Agyemang C; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Ärnlöv J; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  • Aziz NA; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
  • Baccarelli A; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
  • Bochud M; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Brenner H; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Bressler J; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Breteler MMB; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Carmeli C; Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ, Amsterdam, the Netherlands.
  • Chaker L; Department of Neurobiology, Care Sciences and Society (NVS), Family Medicine and Primary Care Unit, Karolinska Institutet, Huddinge, Sweden.
  • Coresh J; School of Health and Social Studies, Dalarna University, Falun, Sweden.
  • Corre T; Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Correa A; Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Cox SR; Laboratory of Environmental Precision Health, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Delgado GE; Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
  • Eckardt KU; German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
  • Ekici AB; Network Aging Research, Heidelberg University, Heidelberg, Germany.
  • Endlich K; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Floyd JS; German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fraszczyk E; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
  • Gao X; Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Gào X; Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Gelber AC; Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
  • Ghanbari M; Population Health Laboratory, University of Fribourg, Fribourg, Switzerland.
  • Ghasemi S; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Gieger C; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Greenland P; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Grove ML; Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
  • Harris SE; Department of Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
  • Hemani G; Lothian Birth Cohorts Group, Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Henneman P; Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Herder C; Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.
  • Horvath S; Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Hou L; Institute of Human Genetics, Friedrich-Alexander-UniversitätErlangen-Nürnberg, 91054, Erlangen, Germany.
  • Hurme MA; Department of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
  • Hwang SJ; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
  • Kardia SLR; Department of Medicine, University of Washington, Seattle, 98101, WA, USA.
Nat Commun ; 12(1): 7173, 2021 12 09.
Article em En | MEDLINE | ID: mdl-34887389
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Úrico / Proteínas Facilitadoras de Transporte de Glucose / Epigenoma / Gota Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Úrico / Proteínas Facilitadoras de Transporte de Glucose / Epigenoma / Gota Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido