Genetics and beyond--the transcriptome of human monocytes and disease susceptibility
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Genetics and beyond--the transcriptome of human monocytes and disease susceptibility. / Zeller, Tanja; Wild, Philipp; Szymczak, Silke; Rotival, Maxime; Schillert, Arne; Castagne, Raphaele; Maouche, Seraya; Germain, Marine; Lackner, Karl; Rossmann, Heidi; Eleftheriadis, Medea; Sinning, Christoph R; Schnabel, Renate B; Lubos, Edith; Mennerich, Detlev; Rust, Werner; Perret, Claire; Proust, Carole; Nicaud, Viviane; Loscalzo, Joseph; Hübner, Norbert; Tregouet, David; Münzel, Thomas; Ziegler, Andreas; Tiret, Laurence; Blankenberg, Stefan; Cambien, François.
in: PLOS ONE, Jahrgang 5, Nr. 5, 18.05.2010, S. e10693.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetics and beyond--the transcriptome of human monocytes and disease susceptibility
AU - Zeller, Tanja
AU - Wild, Philipp
AU - Szymczak, Silke
AU - Rotival, Maxime
AU - Schillert, Arne
AU - Castagne, Raphaele
AU - Maouche, Seraya
AU - Germain, Marine
AU - Lackner, Karl
AU - Rossmann, Heidi
AU - Eleftheriadis, Medea
AU - Sinning, Christoph R
AU - Schnabel, Renate B
AU - Lubos, Edith
AU - Mennerich, Detlev
AU - Rust, Werner
AU - Perret, Claire
AU - Proust, Carole
AU - Nicaud, Viviane
AU - Loscalzo, Joseph
AU - Hübner, Norbert
AU - Tregouet, David
AU - Münzel, Thomas
AU - Ziegler, Andreas
AU - Tiret, Laurence
AU - Blankenberg, Stefan
AU - Cambien, François
PY - 2010/5/18
Y1 - 2010/5/18
N2 - BACKGROUND: Variability of gene expression in human may link gene sequence variability and phenotypes; however, non-genetic variations, alone or in combination with genetics, may also influence expression traits and have a critical role in physiological and disease processes.METHODOLOGY/PRINCIPAL FINDINGS: To get better insight into the overall variability of gene expression, we assessed the transcriptome of circulating monocytes, a key cell involved in immunity-related diseases and atherosclerosis, in 1,490 unrelated individuals and investigated its association with >675,000 SNPs and 10 common cardiovascular risk factors. Out of 12,808 expressed genes, 2,745 expression quantitative trait loci were detected (P<5.78x10(-12)), most of them (90%) being cis-modulated. Extensive analyses showed that associations identified by genome-wide association studies of lipids, body mass index or blood pressure were rarely compatible with a mediation by monocyte expression level at the locus. At a study-wide level (P<3.9x10(-7)), 1,662 expression traits (13.0%) were significantly associated with at least one risk factor. Genome-wide interaction analyses suggested that genetic variability and risk factors mostly acted additively on gene expression. Because of the structure of correlation among expression traits, the variability of risk factors could be characterized by a limited set of independent gene expressions which may have biological and clinical relevance. For example expression traits associated with cigarette smoking were more strongly associated with carotid atherosclerosis than smoking itself.CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the monocyte transcriptome is a potent integrator of genetic and non-genetic influences of relevance for disease pathophysiology and risk assessment.
AB - BACKGROUND: Variability of gene expression in human may link gene sequence variability and phenotypes; however, non-genetic variations, alone or in combination with genetics, may also influence expression traits and have a critical role in physiological and disease processes.METHODOLOGY/PRINCIPAL FINDINGS: To get better insight into the overall variability of gene expression, we assessed the transcriptome of circulating monocytes, a key cell involved in immunity-related diseases and atherosclerosis, in 1,490 unrelated individuals and investigated its association with >675,000 SNPs and 10 common cardiovascular risk factors. Out of 12,808 expressed genes, 2,745 expression quantitative trait loci were detected (P<5.78x10(-12)), most of them (90%) being cis-modulated. Extensive analyses showed that associations identified by genome-wide association studies of lipids, body mass index or blood pressure were rarely compatible with a mediation by monocyte expression level at the locus. At a study-wide level (P<3.9x10(-7)), 1,662 expression traits (13.0%) were significantly associated with at least one risk factor. Genome-wide interaction analyses suggested that genetic variability and risk factors mostly acted additively on gene expression. Because of the structure of correlation among expression traits, the variability of risk factors could be characterized by a limited set of independent gene expressions which may have biological and clinical relevance. For example expression traits associated with cigarette smoking were more strongly associated with carotid atherosclerosis than smoking itself.CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the monocyte transcriptome is a potent integrator of genetic and non-genetic influences of relevance for disease pathophysiology and risk assessment.
KW - Adult
KW - Aged
KW - Atherosclerosis/genetics
KW - Base Sequence
KW - Cell Movement/genetics
KW - Chromosomes, Human, Pair 21/genetics
KW - DNA Probes/metabolism
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome, Human/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Immunity/genetics
KW - Male
KW - Middle Aged
KW - Monocytes/cytology
KW - Phenotype
KW - Polymorphism, Single Nucleotide/genetics
KW - Quantitative Trait Loci/genetics
KW - Quantitative Trait, Heritable
KW - Risk Factors
KW - Smoking/adverse effects
U2 - 10.1371/journal.pone.0010693
DO - 10.1371/journal.pone.0010693
M3 - SCORING: Journal article
C2 - 20502693
VL - 5
SP - e10693
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 5
ER -