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PLoS Genet. 2015 Mar 18;11(3):e1005035. doi: 10.1371/journal.pgen.1005035. eCollection 2015.

A meta-analysis of gene expression signatures of blood pressure and hypertension.

Author information

  • 1The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America.
  • 2Estonian Genome Center, University of Tartu, Tartu, Estonia; Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
  • 3Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands; Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden and Rotterdam, The Netherlands.
  • 4Epidemiology and Public Health Group, Medical School, University of Exeter, Exeter, United Kingdom.
  • 5Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, München, Germany.
  • 6Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity & Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • 7The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America; Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; Hebrew SeniorLife, Boston, Boston, Massachusetts, United States of America.
  • 8The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America; Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland, United States of America.
  • 9Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 10Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • 11Division of Geriatrics and Clinical Gerontology National Institute on Aging, Bethesda, Maryland, United States of America.
  • 12Genomics Core facility Genetics & Developmental Biology Center, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America.
  • 13Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden and Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
  • 14Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands; Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden and Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
  • 15Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, United States of America.
  • 16Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
  • 17Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
  • 18Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), Partner Munich, Munich, Germany.
  • 19Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, München, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
  • 20Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), Partner Munich, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
  • 21Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
  • 22Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • 23University Medicine Greifswald, Department of Internal Medicine B-Cardiology, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • 24Universitäres Herzzentrum Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
  • 25The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America.
  • 26Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States of America.
  • 27Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • 28Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

Abstract

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

PMID:
25785607
[PubMed - indexed for MEDLINE]
PMCID:
PMC4365001
Free PMC Article
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