Evidence map›Paper›PMID 24604202›Full record

ArticleScience (New York, N.Y.)2014

Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

Benjamin P Fairfax, Peter Humburg, Seiko Makino, Vivek Naranbhai, Daniel Wong, Evelyn Lau, Luke Jostins, Katharine Plant, Robert Andrews, Chris McGee and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 486 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
486citing papers in PubMed, 8 pooled it
61.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

486 citing papers in PubMed, 8 syntheses or guidelines pooled it, 828 citations in OpenAlex.

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426 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 2 countries.

Benjamin P FairfaxWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Peter Humburg *Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Seiko Makino *Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Vivek NaranbhaiWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Daniel WongWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Evelyn LauWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Luke JostinsWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Katharine PlantWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Robert AndrewsWellcome Trust Sanger Institute, University of Cambridge, Hinxton CB10 1SA, UK.
Chris McGeeWellcome Trust Sanger Institute, University of Cambridge, Hinxton CB10 1SA, UK.
Julian C KnightWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Centre for Human Genetics · GB

Funding

European Research Council 281824Medical Research Council 98082Medical Research Council G1001708Wellcome Trust 074318Wellcome Trust 088891Wellcome Trust 090532Wellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.

Indexed as

Genetic Predisposition to DiseaseAdultAryl Hydrocarbon HydroxylasesBasic-Leucine Zipper Transcription FactorsCARD Signaling Adaptor ProteinsChromosome MappingCrohn DiseaseCytochrome P-450 CYP1B1FemaleGene Expression RegulationGenetic VariationGenome-Wide Association StudyHumansImmunity, InnateIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaAryl Hydrocarbon HydroxylasesBasic-Leucine Zipper Transcription FactorsCARD9 protein, humanCARD Signaling Adaptor ProteinsCYP1B1 protein, humanCytochrome P-450 CYP1B1IDO2 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterferon Regulatory Factor-2Interferon Regulatory Factor-8Interferon Regulatory FactorsIRF2 protein, humanLipopolysaccharide ReceptorsNFE2L3 protein, humanP2RY11 protein, humanReceptors, Purinergic P2

Identifiers

PMID24604202
PMCPMC4064786
OpenAlexW2012697072

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.