Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure

Tanja Zeller, Claudia Schurmann, Katharina Schramm, Christian Müller, Soonil Kwon, Philipp S Wild, Alexander Teumer, David Herrington, Arne Schillert, Licia Iacoviello, Adelheid Kratzer, Annika Jagodzinski, Mahir Karakas, Jingzhong Ding, Johannes T Neumann, Kari Kuulasmaa, Christian Gieger, Tim Kacprowski, Renate B Schnabel, Michael RodenSimone Wahl, Jerome I Rotter, Francisco Ojeda, Maren Carstensen-Kirberg, David-Alexandre Tregouet, Marcus Dörr, Thomas Meitinger, Karl J Lackner, Petra Wolf, Stephan B Felix, Ulf Landmesser, Simona Costanzo, Andreas Ziegler, Yongmei Liu, Uwe Völker, Walter Palmas, Holger Prokisch, Xiuqing Guo, Christian Herder, Stefan Blankenberg, Georg Homuth

Research output: Contribution to journalArticle

Abstract

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, and TPPP3) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P=5.0×10-5). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.

Original languageEnglish
Pages (from-to)743-750
Number of pages8
JournalHypertension
Volume70
Issue number4
DOIs
Publication statusPublished - Oct 2017

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Keywords

  • Adult
  • Blood Pressure
  • Blood Pressure Determination
  • CCAAT-Enhancer-Binding Proteins
  • Carrier Proteins
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Humans
  • Hypertension
  • LIM Domain Proteins
  • Male
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Poly(ADP-ribose) Polymerases
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Stroke
  • Transcription Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Zeller, T., Schurmann, C., Schramm, K., Müller, C., Kwon, S., Wild, P. S., Teumer, A., Herrington, D., Schillert, A., Iacoviello, L., Kratzer, A., Jagodzinski, A., Karakas, M., Ding, J., Neumann, J. T., Kuulasmaa, K., Gieger, C., Kacprowski, T., Schnabel, R. B., ... Homuth, G. (2017). Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure. Hypertension, 70(4), 743-750. https://doi.org/10.1161/HYPERTENSIONAHA.117.09458