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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N; Saleheen, Danish; Lehne, Benjamin; Leach, Irene Mateo; Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Yu Mok, Zuan; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W.
Afiliación
  • Kato N; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Loh M; Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Takeuchi F; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Verweij N; Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore.
  • Wang X; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Zhang W; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Kelly TN; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
  • Saleheen D; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Lehne B; Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.
  • Leach IM; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
  • Drong AW; Center for Non-Communicable Diseases, Karachi, Pakistan.
  • Abbott J; Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Wahl S; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Tan ST; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Scott WR; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Campanella G; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Chadeau-Hyam M; Bioinformatics Support Service, Imperial College London, London, UK.
  • Afzal U; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Ahluwalia TS; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Bonder MJ; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Chen P; Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.
  • Dehghan A; National Heart and Lung Institute, Imperial College London, London, UK.
  • Edwards TL; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Esko T; National Heart and Lung Institute, Imperial College London, London, UK.
  • Go MJ; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Harris SE; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Hartiala J; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Kasela S; Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.
  • Kasturiratne A; Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Khor CC; Copenhagen Prospective Studies on Asthma in Childhood (COSPAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Kleber ME; Steno Diabetes Center, Gentofte, Denmark.
  • Li H; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Yu Mok Z; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
  • Nakatochi M; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Sapari NS; Vanderbilt Epidemiology Center, Center for Human Genetics Research, Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
  • Saxena R; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Stewart AFR; Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts, USA.
  • Stolk L; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  • Tabara Y; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Teh AL; Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
  • Wu Y; Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and Medical Research Council (MRC) Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
  • Wu JY; Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Zhang Y; Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
  • Aits I; Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
  • Da Silva Couto Alves A; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Das S; Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
  • Dorajoo R; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
  • Hopewell JC; Genome Institute of Singapore, ASTAR, Singapore.
  • Kim YK; Department of Ophthalmology, National University of Singapore, Singapore.
  • Koivula RW; Department of Paediatrics, National University of Singapore, Singapore.
Nat Genet ; 47(11): 1282-1293, 2015 11.
Article en En | MEDLINE | ID: mdl-26390057
ABSTRACT
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Presión Sanguínea / Metilación de ADN / Estudio de Asociación del Genoma Completo / Sitios Genéticos Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Presión Sanguínea / Metilación de ADN / Estudio de Asociación del Genoma Completo / Sitios Genéticos Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article