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Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility

Open access
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·2010·PLoS ONE

Abstract

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.

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Metadata

Authors
Zeller, T., Wild, P., Szymczak, S., Rotival, M., Schillert, A., Castagne, R., Maouche, S., Germain, M., Lackner, K., Rossmann, H., Eleftheriadis, M., Sinning, C. R., Schnabel, R. B., Lubos, E., Mennerich, D., Rust, W., Perret, C., Proust, C., Nicaud, V., Loscalzo, J., Hübner, N., Tregouet, D., Münzel, T., Ziegler, A., Tiret, L., Blankenberg, S., & Cambien, F.
Venue
PLoS ONE
Published
2010-05-18
Volume
5
Issue
5
Pages
e10693
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1984939442
Cited by
589
References
15
FWCI
32.36
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility. https://app.cochat.ai/papers/10.1371/journal.pone.0010693
The paper
Zeller, T., Wild, P., Szymczak, S., Rotival, M., Schillert, A., Castagne, R., Maouche, S., Germain, M., Lackner, K., Rossmann, H., Eleftheriadis, M., Sinning, C. R., Schnabel, R. B., Lubos, E., Mennerich, D., Rust, W., Perret, C., Proust, C., Nicaud, V., . . . Cambien, F. (2010). Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility. PLoS ONE. https://doi.org/10.1371/journal.pone.0010693

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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