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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität Mainz, Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Philipp
authors.initials: P
authors.lastname: Wild
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.forename: Maxime
authors.initials: M
authors.lastname: Rotival
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.forename: Raphaele
authors.initials: R
authors.lastname: Castagne
authors.forename: Seraya
authors.initials: S
authors.lastname: Maouche
authors.forename: Marine
authors.initials: M
authors.lastname: Germain
authors.forename: Karl
authors.initials: K
authors.lastname: Lackner
authors.forename: Heidi
authors.initials: H
authors.lastname: Rossmann
authors.forename: Medea
authors.initials: M
authors.lastname: Eleftheriadis
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Edith
authors.initials: E
authors.lastname: Lubos
authors.forename: Detlev
authors.initials: D
authors.lastname: Mennerich
authors.forename: Werner
authors.initials: W
authors.lastname: Rust
authors.forename: Claire
authors.initials: C
authors.lastname: Perret
authors.forename: Carole
authors.initials: C
authors.lastname: Proust
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.forename: David
authors.initials: D
authors.lastname: Tregouet
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: François
authors.initials: F
authors.lastname: Cambien
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics; D001483:Base Sequence; D002465:Cell Movement / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D015342:DNA Probes / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007109:Immunity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
chemical_list: D015342:DNA Probes