A meta-analysis of gene expression signatures of blood pressure and hypertension.
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Authors
Huan, Tianxiao
Peters, Marjolein J
Schramm, Katharina
Chen, Brian H
Liu, Chunyu
Joehanes, Roby
Johnson, Andrew D
Yao, Chen
Ying, Sai-Xia
Courchesne, Paul
Raghavachari, Nalini
Liu, Poching
Reinmaa, Eva
Hofman, Albert
Uitterlinden, André G
Hernandez, Dena G
Bandinelli, Stefania
Singleton, Andrew
Metspalu, Andres
Carstensen, Maren
Grallert, Harald
Herder, Christian
Peters, Annette
Roden, Michael
Waldenberger, Melanie
Felix, Stephan B
International Consortium for Blood Pressure GWAS (ICBP)
Vasan, Ramachandran
O'Donnell, Christopher J
Munson, Peter J
Yang, Xia
van Meurs, Joyce BJ
Ferrucci, Luigi
Publication Date
2015-03Journal Title
PLoS Genet
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Volume
11
Issue
3
Pages
e1005035
Language
eng
Type
Article
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Huan, T., Esko, T., Peters, M. J., Pilling, L. C., Schramm, K., Schurmann, C., Chen, B. H., et al. (2015). A meta-analysis of gene expression signatures of blood pressure and hypertension.. PLoS Genet, 11 (3), e1005035. https://doi.org/10.1371/journal.pgen.1005035
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.
Keywords
International Consortium for Blood Pressure GWAS (ICBP), Humans, Hypertension, Genetic Predisposition to Disease, Gene Expression Regulation, Blood Pressure, Genotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Transcriptome
Identifiers
External DOI: https://doi.org/10.1371/journal.pgen.1005035
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280626
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