Evidence map›Paper›PMID 28340599›Full record

ArticleGenome medicine2017

DNA methylation changes at infertility genes in newborn twins conceived by in vitro fertilisation.

Juan E Castillo-Fernandez, Yuk Jing Loke, Sebastian Bass-Stringer, Fei Gao, Yudong Xia, Honglong Wu, Hanlin Lu, Yuan Liu, Jun Wang, Tim D Spector and 3 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 2% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Epigenetic Risks of Medically Assisted Reproduction.Journal of clinical medicine · 2022
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. DNA methylation differences at birth after conception through ART.Human reproduction (Oxford, England) · 2021
    Article
  18. Article
  19. Article
  20. 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 6 institutions in 5 countries.

Juan E Castillo-FernandezDepartment of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH, London, UK.
Yuk Jing LokeEarly Life Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.
Sebastian Bass-StringerEarly Life Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.
Fei GaoBGI-Shenzhen, Shenzhen, China.
Yudong XiaBGI-Shenzhen, Shenzhen, China.
Honglong WuBGI-Shenzhen, Shenzhen, China.
Hanlin LuBGI-Shenzhen, Shenzhen, China.
Yuan LiuBGI-Shenzhen, Shenzhen, China.
Jun WangBGI-Shenzhen, Shenzhen, China.
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH, London, UK. tim.spector@kcl.ac.uk.
Richard SafferyDepartment of Paediatrics, University of Melbourne, Parkville, VIC, Australia. richard.saffery@mcri.edu.au.
Jeffrey M CraigEarly Life Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia. jeff.craig@mcri.edu.au.
Jordana T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH, London, UK. jordana.bell@kcl.ac.uk.
BGI Group (China) · CNKing's College London · GBUniversity of Melbourne · AUKing Abdulaziz University · SAMurdoch Children's Research Institute · AURoyal Children's Hospital · AU

Funding

Biotechnology and Biological Sciences Research CouncilEuropean Research Council 250157Wellcome Trust
6 · The paper itself

Abstract

backgroundThe association of in vitro fertilisation (IVF) and DNA methylation has been studied predominantly at regulatory regions of imprinted genes and at just thousands of the ~28 million CpG sites in the human genome.

methodsWe investigated the links between IVF and DNA methylation patterns in whole cord blood cells (n = 98) and cord blood mononuclear cells (n = 82) from newborn twins using genome-wide methylated DNA immunoprecipitation coupled with deep sequencing.

resultsAt a false discovery rate (FDR) of 5%, we identified one significant whole blood DNA methylation change linked to conception via IVF, which was located ~3 kb upstream of TNP1, a gene previously linked to male infertility. The 46 most strongly associated signals (FDR of 25%) included a second region in a gene also previously linked to infertility, C9orf3, suggesting that our findings may in part capture the effect of parental subfertility. Using twin modelling, we observed that individual-specific environmental factors appear to be the main overall contributors of methylation variability at the FDR 25% IVF-associated differentially methylated regions, although evidence for methylation heritability was also obtained at several of these regions. We replicated previous findings of differential methylation associated with IVF at the H19/IGF2 region in cord blood mononuclear cells, and we validated the signal at C9orf3 in monozygotic twins. We also explored the impact of intracytoplasmic sperm injection on the FDR 25% signals for potential effects specific to male or female infertility factors.

conclusionsTo our knowledge, this is the most comprehensive study of DNA methylation profiles at birth and IVF conception to date, and our results show evidence for epigenetic modifications that may in part reflect parental subfertility.

Indexed as

DNA MethylationEpigenesis, GeneticFertilization in VitroGenome, HumanTwinsAminopeptidasesBlood CellsChromosomal Proteins, Non-HistoneFemaleFetal BloodHumansInfant, NewbornInfertilityMaleAminopeptidasesAOPEP protein, humanChromosomal Proteins, Non-Histonespermatid transition proteinsDNA methylationEpigenomicsIn vitro fertilisation (IVF)MeDIP-seq

Identifiers

PMID28340599
PMCPMC5364659
OpenAlexW2599208506

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LicenceCC BY
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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.