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Huan, T.* ; Esko, T.* ; Peters, M.J.* ; Pilling, L.C.* ; Schramm, K. ; Schurmann, C.* ; Chen, B.H.* ; Liu, C.* ; Joehanes, R.* ; Johnson, A.D.* ; Yao, C.* ; Ying, S.X.* ; Courchesne, P.* ; Milani, L.* ; Raghavachari, N.* ; Wang, R.* ; Liu, P.* ; Reinmaa, E.* ; Dehghan, A.* ; Hofman, A.* ; Uitterlinden, A.G.* ; Hernandez, D.G.* ; Bandinelli, S.* ; Singleton, A.* ; Melzer, D.* ; Metspalu, A.* ; Carstensen, M.* ; Grallert, H. ; Herder, C.* ; Meitinger, T. ; Peters, A. ; Roden, M.* ; Waldenberger, M. ; Dörr, M.* ; Felix, S.B.* ; Zeller, T.* ; ICBP Consortium (Levy, D.*) ; Vasan, R.S.* ; O'Donnell, C.J.* ; Munson, P.J.* ; Yang, X.* ; Prokisch, H. ; Völker, U.* ; van Meurs, J.B.* ; Ferrucci, L.*

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

PLoS Genet. 11:e1005035 (2015)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Peripheral-blood; Microarray Analysis; Potassium; Cells; Prevention; Profile; Sodium; Trials; Mice
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 11, Issue: 3, Pages: , Article Number: e1005035 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place San Francisco
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-501900-071
G-504091-002
G-504091-001
G-500700-001
G-504000-001
G-501900-401
G-501900-402
PubMed ID 25785607
DOI 10.1371/journal.pgen.1005035
WOS ID WOS:000352197100027
Scopus ID 84989801107
Erfassungsdatum 2015-03-20
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