Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure
Standard
Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure. / Zeller, Tanja; Schurmann, Claudia; Schramm, Katharina; Müller, Christian; Kwon, Soonil; Wild, Philipp S; Teumer, Alexander; Herrington, David; Schillert, Arne; Iacoviello, Licia; Kratzer, Adelheid; Jagodzinski, Annika; Karakas, Mahir; Ding, Jingzhong; Neumann, Johannes T; Kuulasmaa, Kari; Gieger, Christian; Kacprowski, Tim; Schnabel, Renate B; Roden, Michael; Wahl, Simone; Rotter, Jerome I; Ojeda, Francisco; Carstensen-Kirberg, Maren; Tregouet, David-Alexandre; Dörr, Marcus; Meitinger, Thomas; Lackner, Karl J; Wolf, Petra; Felix, Stephan B; Landmesser, Ulf; Costanzo, Simona; Ziegler, Andreas; Liu, Yongmei; Völker, Uwe; Palmas, Walter; Prokisch, Holger; Guo, Xiuqing; Herder, Christian; Blankenberg, Stefan; Homuth, Georg.
in: HYPERTENSION, Jahrgang 70, Nr. 4, 10.2017, S. 743-750.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure
AU - Zeller, Tanja
AU - Schurmann, Claudia
AU - Schramm, Katharina
AU - Müller, Christian
AU - Kwon, Soonil
AU - Wild, Philipp S
AU - Teumer, Alexander
AU - Herrington, David
AU - Schillert, Arne
AU - Iacoviello, Licia
AU - Kratzer, Adelheid
AU - Jagodzinski, Annika
AU - Karakas, Mahir
AU - Ding, Jingzhong
AU - Neumann, Johannes T
AU - Kuulasmaa, Kari
AU - Gieger, Christian
AU - Kacprowski, Tim
AU - Schnabel, Renate B
AU - Roden, Michael
AU - Wahl, Simone
AU - Rotter, Jerome I
AU - Ojeda, Francisco
AU - Carstensen-Kirberg, Maren
AU - Tregouet, David-Alexandre
AU - Dörr, Marcus
AU - Meitinger, Thomas
AU - Lackner, Karl J
AU - Wolf, Petra
AU - Felix, Stephan B
AU - Landmesser, Ulf
AU - Costanzo, Simona
AU - Ziegler, Andreas
AU - Liu, Yongmei
AU - Völker, Uwe
AU - Palmas, Walter
AU - Prokisch, Holger
AU - Guo, Xiuqing
AU - Herder, Christian
AU - Blankenberg, Stefan
AU - Homuth, Georg
N1 - © 2017 American Heart Association, Inc.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Adult
KW - Blood Pressure/genetics
KW - Blood Pressure Determination/methods
KW - CCAAT-Enhancer-Binding Proteins/genetics
KW - Carrier Proteins/genetics
KW - Female
KW - Gene Expression
KW - Gene Expression Profiling
KW - Genome-Wide Association Study
KW - Humans
KW - Hypertension/diagnosis
KW - LIM Domain Proteins/genetics
KW - Male
KW - Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics
KW - Poly(ADP-ribose) Polymerases/genetics
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Stroke/epidemiology
KW - Transcription Factors/genetics
U2 - 10.1161/HYPERTENSIONAHA.117.09458
DO - 10.1161/HYPERTENSIONAHA.117.09458
M3 - SCORING: Journal article
C2 - 28784648
VL - 70
SP - 743
EP - 750
JO - HYPERTENSION
JF - HYPERTENSION
SN - 0194-911X
IS - 4
ER -