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

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.

• Authors: Tianxiao Huan, Tõnu Esko, Marjolein J Peters, Luke C Pilling, Katharina Schramm, Claudia Schurmann, Brian H Chen, Chunyu Liu, Roby Joehanes, Andrew D Johnson, Chen Yao, Sai-Xia Ying, Paul Courchesne, Lili Milani, Nalini Raghavachari, Richard Wang, Poching Liu, Eva Reinmaa, Abbas Dehghan, Albert Hofman, André G Uitterlinden, Dena G Hernandez, Stefania Bandinelli, Andrew Singleton, David Melzer, Andres Metspalu, Maren Carstensen, Harald Grallert, Christian Herder, Thomas Meitinger, Annette Peters, Michael Roden, Melanie Waldenberger, Marcus Dörr, Stephan B Felix, Tanja Zeller, International Consortium for Blood Pressure GWAS (ICBP), Ramachandran Vasan, Christopher J O'Donnell, Peter J Munson, Xia Yang, Holger Prokisch, Uwe Völker, Joyce B J van Meurs, Luigi Ferrucci, Daniel Levy
• Journal: PLoS genetics (PLoS Genet) Vol. 11 Issue 3 Pg. e1005035 (Mar 2015) ISSN: 1553-7404 [Electronic] United States
• PMID: 25785607 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Blood Pressure (genetics)
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Hypertension (genetics, pathology)
• Polymorphism, Single Nucleotide
• Transcriptome (genetics)