Evidence map›Paper›PMID 33739972›Full record

ArticlePLoS genetics2021

Assessing the co-variability of DNA methylation across peripheral cells and tissues: Implications for the interpretation of findings in epigenetic epidemiology.

Eilis Hannon, Georgina Mansell, Emma Walker, Marta F Nabais, Joe Burrage, Agnieszka Kepa, Janis Best-Lane, Anna Rose, Suzanne Heck, Terrie E Moffitt and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

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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

13 authors at 7 institutions in 3 countries.

Eilis HannonUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.ORCID 0000-0001-6840-072X
Georgina MansellUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.ORCID 0000-0003-2620-1786
Emma WalkerUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.ORCID 0000-0003-2222-4577
Marta F NabaisUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.ORCID 0000-0002-9545-5889
Joe BurrageUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
Agnieszka KepaSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Janis Best-LaneSection of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom.ORCID 0000-0003-2528-898X
Anna RoseBRC Flow Cytometry Platform, NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0003-2854-7377
Suzanne HeckBiomedical Research Centre at Guy's and St Thomas' Hospitals and King's College London, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Terrie E MoffittSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Avshalom CaspiSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.ORCID 0000-0003-0082-4600
Louise ArseneaultSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.ORCID 0000-0002-2938-2191
Jonathan MillUniversity of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.ORCID 0000-0003-1115-3224
University of Exeter · GBDuke University · USKing's College London · GBGuy's and St Thomas' NHS Foundation Trust · GBImperial College Healthcare NHS Trust · GBSt Thomas' Hospital · GBThe University of Queensland · AU

Funding

Neuropsychological and genomic signatures of violence exposure in childhoodR01HD077482 · NICHD · DUKE UNIVERSITY · PI CASPI, AVSHALOM · 2013 to 2018
$2.8M
Medical Research Council G1002190Medical Research Council K013807Medical Research Council M008924Medical Research Council MR/M008924/1NICHD NIH HHS R01 HD077482
6 · The paper itself

Abstract

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an individual cellular population. We collected three peripheral tissues (whole blood, buccal epithelial and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4+ T cells, CD8+ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. We identified significant differences in both the level and variability of DNAm between different sample types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, although the proportion of variance explained was greater than that explained by either buccal or nasal epithelial samples. Covariation across sample types was much higher for DNAm sites influenced by genetic factors. Overall, we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites, however, variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight about EWAS findings. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and our data will facilitate the interpretation of findings in epigenetic epidemiology.

Indexed as

DNA MethylationEpigenesis, GeneticEpigenomicsMolecular EpidemiologyBlood CellsGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansOrgan SpecificityTranscriptome

Identifiers

PMID33739972
PMCPMC8011804
OpenAlexW3135913256

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.