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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, Vol. 5, No. 5, 18.05.2010, p. e10693.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zeller, T, Wild, P, Szymczak, S, Rotival, M, Schillert, A, Castagne, R, Maouche, S, Germain, M, Lackner, K, Rossmann, H, Eleftheriadis, M, Sinning, CR, Schnabel, RB, 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 2010, 'Genetics and beyond--the transcriptome of human monocytes and disease susceptibility', PLOS ONE, vol. 5, no. 5, pp. e10693. https://doi.org/10.1371/journal.pone.0010693

APA

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, 5(5), e10693. https://doi.org/10.1371/journal.pone.0010693

Vancouver

Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R et al. Genetics and beyond--the transcriptome of human monocytes and disease susceptibility. PLOS ONE. 2010 May 18;5(5):e10693. https://doi.org/10.1371/journal.pone.0010693

Bibtex

@article{0d6ad0a41bb345efb05250ef785d761d,
title = "Genetics and beyond--the transcriptome of human monocytes and disease susceptibility",
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.",
keywords = "Adult, Aged, Atherosclerosis/genetics, Base Sequence, Cell Movement/genetics, Chromosomes, Human, Pair 21/genetics, DNA Probes/metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Genetic Variation, Genome, Human/genetics, Genome-Wide Association Study, Humans, Immunity/genetics, Male, Middle Aged, Monocytes/cytology, Phenotype, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Quantitative Trait, Heritable, Risk Factors, Smoking/adverse effects",
author = "Tanja Zeller and Philipp Wild and Silke Szymczak and Maxime Rotival and Arne Schillert and Raphaele Castagne and Seraya Maouche and Marine Germain and Karl Lackner and Heidi Rossmann and Medea Eleftheriadis and Sinning, {Christoph R} and Schnabel, {Renate B} and Edith Lubos and Detlev Mennerich and Werner Rust and Claire Perret and Carole Proust and Viviane Nicaud and Joseph Loscalzo and Norbert H{\"u}bner and David Tregouet and Thomas M{\"u}nzel and Andreas Ziegler and Laurence Tiret and Stefan Blankenberg and Fran{\c c}ois Cambien",
year = "2010",
month = may,
day = "18",
doi = "10.1371/journal.pone.0010693",
language = "English",
volume = "5",
pages = "e10693",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

RIS

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 -