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Zeller, T.* ; Schurmann, C.* ; Schramm, K. ; Müller, C.* ; Kwon, S.Y.* ; 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.* ; Roden, M.* ; Wahl, S. ; Rotter, J.I.* ; Ojeda, F.* ; Carstensen-Kirberg, M.* ; Tregouet, D.A.* ; Dörr, M.* ; Meitinger, T. ; Lackner, K.J.* ; Wolf, P.A.* ; Felix, S.B.* ; Landmesser, U.* ; Costanzo, S.* ; Ziegler, A.* ; Liu, Y.* ; Völker, U.* ; Palmas, W.* ; Prokisch, H. ; Guo, X.* ; Herder, C.* ; Blankenberg, S.* ; Homuth, G.*

Transcriptome-wide analysis identifies novel associations with blood pressure.

Hypertension 70, 713-750 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Blood Pressure ; Gene Expression ; Genome-wide Association Study ; Hypertension ; Transcriptome; Chronic Kidney-disease; Cardiovascular-disease; Gene-expression; Common Variants; Binding-protein; Hypertension; Loci; Risk; Metaanalysis; Individuals
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 0194-911x
e-ISSN 1524-4563
Journal Hypertension
Quellenangaben Volume: 70, Issue: 4, Pages: 713-750 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
G-504091-004
DOI 10.1161/HYPERTENSIONAHA.117.09458
WOS ID WOS:000410486300017
Scopus ID 85030611451
PubMed ID 28784648
Erfassungsdatum 2017-09-13
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