TY - JOUR
T1 - A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension
AU - International Consortium for Blood Pressure GWAS (ICBP)
AU - CARDIoGRAM consortium
AU - CKDGen Consortium
AU - KidneyGen Consortium
AU - EchoGen consortium
AU - CHARGE-HF consortium
AU - Huan, Tianxiao
AU - Esko, Tõnu
AU - Peters, Marjolein J.
AU - Pilling, Luke C.
AU - Schramm, Katharina
AU - Schurmann, Claudia
AU - Chen, Brian H.
AU - Liu, Chunyu
AU - Joehanes, Roby
AU - Johnson, Andrew D.
AU - Yao, Chen
AU - Ying, Sai xia
AU - Courchesne, Paul
AU - Milani, Lili
AU - Raghavachari, Nalini
AU - Wang, Richard
AU - Liu, Poching
AU - Reinmaa, Eva
AU - Dehghan, Abbas
AU - Hofman, Albert
AU - Uitterlinden, André G.
AU - Hernandez, Dena G.
AU - Bandinelli, Stefania
AU - Singleton, Andrew
AU - Melzer, David
AU - Metspalu, Andres
AU - Carstensen, Maren
AU - Grallert, Harald
AU - Herder, Christian
AU - Meitinger, Thomas
AU - Peters, Annette
AU - Roden, Michael
AU - Waldenberger, Melanie
AU - Dörr, Marcus
AU - Felix, Stephan B.
AU - Zeller, Tanja
AU - Vasan, Ramachandran S.
AU - O'Donnell, Christopher J.
AU - Munson, Peter J.
AU - Yang, Xia
AU - Prokisch, Holger
AU - Völker, Uwe
AU - van Meurs, Joyce B.J.
AU - Ferrucci, Luigi
AU - Levy, Daniel
AU - Ehret, Georg B.
AU - Munroe, Patricia B.
AU - Rice, Kenneth M.
AU - Bochud, Murielle
AU - Eyheramendy, Susana
PY - 2015/3/18
Y1 - 2015/3/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84989801107&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1005035
DO - 10.1371/journal.pgen.1005035
M3 - Article
C2 - 25785607
AN - SCOPUS:84989801107
SN - 1553-7390
VL - 11
JO - PLoS Genetics
JF - PLoS Genetics
IS - 3
M1 - e1005035
ER -