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Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.
Tragante, Vinicius; Barnes, Michael R; Ganesh, Santhi K; Lanktree, Matthew B; Guo, Wei; Franceschini, Nora; Smith, Erin N; Johnson, Toby; Holmes, Michael V; Padmanabhan, Sandosh; Karczewski, Konrad J; Almoguera, Berta; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C; Farrall, Martin; Fischer, Mary E; Gaunt, Tom R; Gho, Johannes M I H; Gieger, Christian; Goel, Anuj; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E; Mateo Leach, Irene; McDonough, Caitrin W; Meijs, Matthijs F L; Melander, Olle; Nelson, Christopher P; Nolte, Ilja M; Pankratz, Nathan; Price, Tom S; Shaffer, Jonathan; Shah, Sonia; Tomaszewski, Maciej; van der Most, Peter J; Van Iperen, Erik P A; Vonk, Judith M; Witkowska, Kate; Wong, Caroline O L; Zhang, Li; Beitelshees, Amber L; Berenson, Gerald S; Bhatt, Deepak L; Brown, Morris; Burt, Amber; Cooper-DeHoff, Rhonda M; Connell, John M; Cruickshanks, Karen J.
Afiliação
  • Tragante V; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
  • Barnes MR; William Harvey Research Institute National Institute for Health Biomedical Research Unit, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
  • Ganesh SK; Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Genetics, University of Michigan Health System, Ann Arbor, MI 48109, USA.
  • Lanktree MB; Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
  • Guo W; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Franceschini N; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Smith EN; Department of Pediatrics and Rady's Children's Hospital, University of California at San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Johnson T; Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Holmes MV; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Padmanabhan S; BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
  • Karczewski KJ; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Almoguera B; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Barnard J; Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Baumert J; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
  • Chang YP; Departments of Medicine and Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Elbers CC; Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
  • Farrall M; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
  • Fischer ME; Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53726, USA.
  • Gaunt TR; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
  • Gho JM; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
  • Gieger C; Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
  • Goel A; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
  • Gong Y; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL 32610, USA.
  • Isaacs A; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands.
  • Kleber ME; Medical Clinic V, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
  • Mateo Leach I; Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
  • McDonough CW; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL 32610, USA.
  • Meijs MF; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
  • Melander O; Hypertension and Cardiovascular Disease, Department of Clinical Sciences, Lund University, Malmö 20502, Sweden; Centre of Emergency Medicine, Skåne University Hospital, Malmö 20502, Sweden.
  • Nelson CP; Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
  • Nolte IM; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
  • Pankratz N; Institute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Price TS; MRC SGDP Centre, Institute of Psychiatry, London SE5 8AF, UK.
  • Shaffer J; Department of Medicine, Columbia University, New York, NY 10032, USA.
  • Shah S; UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, Kathleen Lonsdale Building, Gower Place, London WC1E 6BT, UK.
  • Tomaszewski M; Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK.
  • van der Most PJ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
  • Van Iperen EP; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, the Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
  • Vonk JM; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
  • Witkowska K; Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Wong CO; Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Zhang L; Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Beitelshees AL; Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Berenson GS; Department of Epidemiology, Tulane University, New Orleans, LA 70118, USA.
  • Bhatt DL; Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Brown M; Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK.
  • Burt A; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA 98195, USA.
  • Cooper-DeHoff RM; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL 32610, USA.
  • Connell JM; University of Dundee, Ninewells Hospital &Medical School, Dundee DD1 9SY, UK.
  • Cruickshanks KJ; Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53726, USA; Department of Population Health Sciences, University of Wisconsin, Madison, WI 53726, USA.
Am J Hum Genet ; 94(3): 349-60, 2014 Mar 06.
Article em En | MEDLINE | ID: mdl-24560520
Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sístole / Pressão Sanguínea / População Branca / Diástole / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans País/Região como assunto: Europa Idioma: En Revista: Am J Hum Genet Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Holanda
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sístole / Pressão Sanguínea / População Branca / Diástole / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans País/Região como assunto: Europa Idioma: En Revista: Am J Hum Genet Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Holanda