Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Immune response eQTL study in primary human monocytes stimulated with multiple microbial ligands under multiple time points

ABSTRACT: Gene expression arrays and genotyping data in primary human monocytes from healthy individuals of European ancestry that have either been unstimulated (baseline), exposed to Lipopolysaccharide (90 minutes or 6 hours duration), muramyl-dipeptide (90 minutes or 6 hours duration) or transfected with 5’-triphosphate RNA (90 minutes or 6 hours duration). Please note that eQTL analysis methods and result files format are available as additional files attached to this experiment ( see https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5631/files/ ).

ORGANISM(S): Homo sapiens

SUBMITTER: Sarah Kim-Hellmuth

PROVIDER: E-MTAB-5631 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes.

Kim Sarah S Becker Jessica J Bechheim Matthias M Kaiser Vera V Noursadeghi Mahdad M Fricker Nadine N Beier Esther E Klaschik Sven S Boor Peter P Hess Timo T Hofmann Andrea A Holdenrieder Stefan S Wendland Jens R JR Fröhlich Holger H Hartmann Gunther G Nöthen Markus M MM Müller-Myhsok Bertram B Pütz Benno B Hornung Veit V Schumacher Johannes J

Nature communications 20141020

Toll-like receptors (TLRs) play a key role in innate immunity. Apart from their function in host defense, dysregulation in TLR signalling can confer risk to autoimmune diseases, septic shock or cancer. Here we report genetic variants and transcripts that are active only during TLR signalling and contribute to interindividual differences in immune response. Comparing unstimulated versus TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci (eQTLs) that are unique to TLR4 stim ...[more]

PMID: 25327457

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Project description:Short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (e.g., genetics and shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of short habitual sleep duration on gene expression. Therefore, we sought to investigate gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration. Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD=18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with two-weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Next, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome. The mean 24 hour sleep duration of the total sample was 439.2 minutes (SD=46.8 minutes; range 325.4 to 521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD=21.2; range 45.9 to 114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion. Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular and inflammatory outcomes.

Dataset Information

Immune response eQTL study in primary human monocytes stimulated with multiple microbial ligands under multiple time points

Publications

Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes.

Similar Datasets

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