dc.contributor.author | Huan, T | |
dc.contributor.author | Esko, T | |
dc.contributor.author | Peters, MJ | |
dc.contributor.author | Pilling, LC | |
dc.contributor.author | Schramm, K | |
dc.contributor.author | Schurmann, C | |
dc.contributor.author | Chen, BH | |
dc.contributor.author | Liu, C | |
dc.contributor.author | Joehanes, R | |
dc.contributor.author | Johnson, AD | |
dc.contributor.author | Yao, C | |
dc.contributor.author | Ying, SX | |
dc.contributor.author | Courchesne, P | |
dc.contributor.author | Milani, L | |
dc.contributor.author | Raghavachari, N | |
dc.contributor.author | Wang, R | |
dc.contributor.author | Liu, P | |
dc.contributor.author | Reinmaa, E | |
dc.contributor.author | Dehghan, A | |
dc.contributor.author | Hofman, A | |
dc.contributor.author | Uitterlinden, AG | |
dc.contributor.author | Hernandez, Dena | |
dc.contributor.author | Bandinelli, S | |
dc.contributor.author | Singleton, A | |
dc.contributor.author | Melzer, D | |
dc.contributor.author | Metspalu, A | |
dc.contributor.author | Carstensen, M | |
dc.contributor.author | Grallert, H | |
dc.contributor.author | Herder, C | |
dc.contributor.author | Meitinger, T | |
dc.contributor.author | Peters, A | |
dc.contributor.author | Roden, M | |
dc.contributor.author | Waldenberger, M | |
dc.contributor.author | Dörr, M | |
dc.contributor.author | Felix, SB | |
dc.contributor.author | Zeller, T | |
dc.contributor.author | International Consortium for Blood Pressure GWAS (ICBP) | |
dc.contributor.author | Vasan, R | |
dc.contributor.author | O'Donnell, CJ | |
dc.contributor.author | Munson, PJ | |
dc.contributor.author | Yang, X | |
dc.contributor.author | Prokisch, H | |
dc.contributor.author | Völker, U | |
dc.contributor.author | van Meurs, JB | |
dc.contributor.author | Ferrucci, L | |
dc.contributor.author | Levy, D | |
dc.date.accessioned | 2015-06-08T14:19:12Z | |
dc.date.issued | 2015-03-18 | |
dc.description.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. | en_GB |
dc.description.sponsorship | National Institutes of Health | en_GB |
dc.description.sponsorship | Estonian Ministry of Science and Education | en_GB |
dc.description.sponsorship | Development Fund of the University of Tartu | en_GB |
dc.description.sponsorship | European Regional Development Fund to the Centre of Excellence in Genomics | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | European Commission’s Seventh Framework Programme | en_GB |
dc.description.sponsorship | Netherlands Organisation of Scientific Research | en_GB |
dc.description.sponsorship | National Institute on Aging | en_GB |
dc.description.sponsorship | German Federal Ministry of Health | en_GB |
dc.identifier.citation | Vol. 11 (3), article e1005035 | en_GB |
dc.identifier.doi | 10.1371/journal.pgen.1005035 | |
dc.identifier.grantnumber | N01-HC-25195 | en_GB |
dc.identifier.grantnumber | SF0180142s08 | en_GB |
dc.identifier.grantnumber | SP1GVARENG | en_GB |
dc.identifier.grantnumber | 3.2.0304.11-0312 | en_GB |
dc.identifier.grantnumber | WT097835MF | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/17450 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/25785607 | en_GB |
dc.rights | This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication | en_GB |
dc.title | A meta-analysis of gene expression signatures of blood pressure and hypertension. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2015-06-08T14:19:12Z | |
dc.identifier.issn | 1553-7390 | |
exeter.place-of-publication | United States | |
dc.description | This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record. | en_GB |
dc.identifier.journal | PLoS Genetics | en_GB |