Evidence map›Paper›PMID 30777123›Full record

Trial reportClinical epigenetics2019

A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57.

Rachelle E Irwin, Sara-Jayne Thursby, Miroslava Ondičová, Kristina Pentieva, Helene McNulty, Rebecca C Richmond, Aoife Caffrey, Diane J Lees-Murdock, Marian McLaughlin, Tony Cassidy and 3 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
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  5. Review
  6. Article
  7. MethylGPT: a foundation model for the DNA methylome.bioRxiv : the preprint server for biology · 2024
    Article
  8. Scientific opinion on the tolerable upper intake level for folate.EFSA journal. European Food Safety Authority · 2023
    Article
  9. Article
  10. Article
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  12. Article
  13. Article
  14. Review
  15. Article
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  17. Review
  18. Review
  19. Article
  20. Nutritional Epigenomics and Age-Related Disease.Current developments in nutrition · 2020
    Article
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 2 institutions in 1 country.

Rachelle E IrwinGenomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.
Sara-Jayne ThursbyGenomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.
Miroslava OndičováGenomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.
Kristina PentievaNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Coleraine, UK.
Helene McNultyNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Coleraine, UK.
Rebecca C RichmondMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Aoife CaffreyNutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Coleraine, UK.
Diane J Lees-MurdockGenomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.
Marian McLaughlinPsychology Institute, Ulster University, Coleraine, UK.
Tony CassidyPsychology Institute, Ulster University, Coleraine, UK.
Matthew SudermanMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Caroline L ReltonMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Colum P WalshGenomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK. cp.walsh@ulster.ac.uk.ORCID 0000-0001-9921-7506
University of Ulster · GBUniversity of Bristol · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MC_UU_00011/5Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/2Medical Research Council MC_UU_12013/8
6 · The paper itself

Abstract

backgroundMaternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86).

resultsThe top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels.

conclusionsThese results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.

Indexed as

AdultDNA-Binding ProteinsDNA MethylationDouble Bind InteractionFemaleFolic AcidGenomic ImprintingHCT116 CellsHumansPregnancyPregnancy Trimester, SecondPregnancy Trimester, ThirdRepressor ProteinsSequence Analysis, DNATranscription FactorsDNA-Binding ProteinsFolic AcidRepressor ProteinsTranscription FactorsZFP57 protein, humanCord bloodDNA methylationFolic acidImprintingOffspringZFP57

Identifiers

PMID30777123
PMCPMC6380035
OpenAlexW2937816548

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.