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

Publication ,  Journal Article
Huan, T; Esko, T; Peters, MJ; Pilling, LC; Schramm, K; Schurmann, C; Chen, BH; Liu, C; Joehanes, R; Johnson, AD; Yao, C; Ying, S-X; Milani, L ...
Published in: PLoS Genet
March 2015

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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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

March 2015

Volume

11

Issue

3

Start / End Page

e1005035

Location

United States

Related Subject Headings

  • Transcriptome
  • Polymorphism, Single Nucleotide
  • Hypertension
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Expression Regulation
  • Developmental Biology
  • Blood Pressure
 

Citation

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Huan, T., Esko, T., Peters, M. J., Pilling, L. C., Schramm, K., Schurmann, C., … Levy, D. (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
Huan, Tianxiao, Tõnu Esko, Marjolein J. Peters, Luke C. Pilling, Katharina Schramm, Claudia Schurmann, Brian H. Chen, et al. “A meta-analysis of gene expression signatures of blood pressure and hypertension.PLoS Genet 11, no. 3 (March 2015): e1005035. https://doi.org/10.1371/journal.pgen.1005035.
Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, et al. A meta-analysis of gene expression signatures of blood pressure and hypertension. PLoS Genet. 2015 Mar;11(3):e1005035.
Huan, Tianxiao, et al. “A meta-analysis of gene expression signatures of blood pressure and hypertension.PLoS Genet, vol. 11, no. 3, Mar. 2015, p. e1005035. Pubmed, doi:10.1371/journal.pgen.1005035.
Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, Chen BH, Liu C, Joehanes R, Johnson AD, Yao C, Ying S-X, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, Hofman A, Uitterlinden AG, Hernandez DG, 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 SB, Zeller T, International Consortium for Blood Pressure GWAS (ICBP), Vasan R, O’Donnell CJ, Munson PJ, Yang X, Prokisch H, Völker U, van Meurs JBJ, Ferrucci L, Levy D. A meta-analysis of gene expression signatures of blood pressure and hypertension. PLoS Genet. 2015 Mar;11(3):e1005035.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

March 2015

Volume

11

Issue

3

Start / End Page

e1005035

Location

United States

Related Subject Headings

  • Transcriptome
  • Polymorphism, Single Nucleotide
  • Hypertension
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene Expression Regulation
  • Developmental Biology
  • Blood Pressure