A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

EchoGen consortium, CHARGE-HF consortium, International Consortium for Blood Pressure GWAS (ICBP), CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1005035
JournalPLoS Genetics
Volume11
Issue number3
DOIs
StatePublished - Mar 18 2015

Fingerprint

hypertension
meta-analysis
Transcriptome
gene expression
blood pressure
Meta-Analysis
blood
Blood Pressure
Hypertension
gene
Genes
Genome-Wide Association Study
Gene Expression
genes
genome
antihypertensive agents
Cyclooxygenase 2
apoptosis
transcriptomics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

EchoGen consortium, CHARGE-HF consortium, International Consortium for Blood Pressure GWAS (ICBP), CARDIoGRAM consortium, CKDGen Consortium, & KidneyGen Consortium (2015). A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension. PLoS Genetics, 11(3), [e1005035]. https://doi.org/10.1371/journal.pgen.1005035

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension. / EchoGen consortium; CHARGE-HF consortium; International Consortium for Blood Pressure GWAS (ICBP); CARDIoGRAM consortium; CKDGen Consortium; KidneyGen Consortium.

In: PLoS Genetics, Vol. 11, No. 3, e1005035, 18.03.2015.

Research output: Contribution to journalArticle

EchoGen consortium, CHARGE-HF consortium, International Consortium for Blood Pressure GWAS (ICBP), CARDIoGRAM consortium, CKDGen Consortium & KidneyGen Consortium 2015, 'A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension', PLoS Genetics, vol. 11, no. 3, e1005035. https://doi.org/10.1371/journal.pgen.1005035
EchoGen consortium, CHARGE-HF consortium, International Consortium for Blood Pressure GWAS (ICBP), CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium. A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension. PLoS Genetics. 2015 Mar 18;11(3). e1005035. https://doi.org/10.1371/journal.pgen.1005035
EchoGen consortium ; CHARGE-HF consortium ; International Consortium for Blood Pressure GWAS (ICBP) ; CARDIoGRAM consortium ; CKDGen Consortium ; KidneyGen Consortium. / A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension. In: PLoS Genetics. 2015 ; Vol. 11, No. 3.
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