Evidence map›Paper›PMID 38663408›Full record

ArticleCell genomics2024

Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.

James J Gilchrist, Hai Fang, Sara Danielli, Marketa Tomkova, Isar Nassiri, Esther Ng, Orion Tong, Chelsea Taylor, Dylan Muldoon, Lea R Z Cohen and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 1 country.

James J GilchristDepartment of Paediatrics, University of Oxford, Oxford OX3 9DU, UK; MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Hai FangCentre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Sara DanielliCentre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Marketa TomkovaLudwig Cancer Research Oxford, University of Oxford, Oxford OX3 7DQ, UK.
Isar NassiriMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Esther NgNuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK.
Orion TongMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Chelsea TaylorMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Dylan MuldoonMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Lea R Z CohenMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Hussein Al-MossawiNuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK.
Evelyn LauCentre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Matt NevilleOxford Centre for Diabetes, Endocrinology, and Metabolism, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LE, UK.
Benjamin Schuster-BoecklerLudwig Cancer Research Oxford, University of Oxford, Oxford OX3 7DQ, UK.
Julian C KnightCentre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Benjamin P FairfaxMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Department of Oncology, University of Oxford, Oxford OX3 9DS, UK. Electronic address: benjamin.fairfax@oncology.ox.ac.uk.
Centre for Human Genetics · GBUniversity of Oxford · GBMRC Weatherall Institute of Molecular Medicine · GBLudwig Cancer Research · GBNuffield Orthopaedic Centre · GBOxford Centre for Diabetes, Endocrinology and Metabolism · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.

Indexed as

CpG IslandsDNA MethylationEpigenesis, GeneticMonocytesAdultAgedFemaleHumansLipopolysaccharidesMaleMiddle AgedLipopolysaccharidescancerDNA methylationepigenetic aginggeneticsinnate immune activationLPSmonocytesmQTL

Identifiers

PMID38663408
PMCPMC11099345
OpenAlexW4395115578

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.