Evidence map›Paper›PMID 22422452›Full record

ArticleInternational journal of epidemiology2012

DNA methylation shows genome-wide association of NFIX, RAPGEF2 and MSRB3 with gestational age at birth.

Hwajin Lee, Andrew E Jaffe, Jason I Feinberg, Rakel Tryggvadottir, Shannon Brown, Carolina Montano, Martin J Aryee, Rafael A Irizarry, Julie Herbstman, Frank R Witter and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of epidemiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 6 pooled it
12.8field-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

47 citing papers in PubMed, 6 syntheses or guidelines pooled it, 75 citations in OpenAlex.

  1. Pooled it
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  7. Trial
  8. Article
  9. Article
  10. The Role of Genetics in Preterm Birth.Reproductive sciences (Thousand Oaks, Calif.) · 2023
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Epigenetic biomarkers and preterm birth.Environmental epigenetics · 2020
    Review
  18. Observational
  19. Exploring insertions and deletions (indels) ofArchives animal breeding · 2019
    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 1 institution in 1 country.

Hwajin LeeCenter for Epigenetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Andrew E Jaffe
Jason I Feinberg
Rakel Tryggvadottir
Shannon Brown
Carolina Montano
Martin J Aryee
Rafael A Irizarry
Julie Herbstman
Frank R Witter
Lynn R Goldman
Andrew P Feinberg
M Daniele Fallin
Johns Hopkins University · US

Funding

Environment, The Perinatal Epigenome, and Risk for Autism and Related DisordersR01ES017646 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI FALLIN, M DANIELE, FEINBERG, ANDREW P. · 2009 to 2013
$8.7M
BWS and Embryonal Tumor Suppressor Genes on 11p15R37CA054358 · NCI · JOHNS HOPKINS UNIVERSITY · PI FEINBERG, ANDREW P. · 2001 to 2009
$4.0M
Novel Approaches to Studying the Situ Bioremediation of Complex MixturesR01ES015445 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI HALDEN, ROLF U · 2006 to 2009
$1.0M
Prenatal PAH exposure and genome-wide methylation in a cohort of sibling-pairsR00ES017051 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HERBSTMAN, JULIE BETH · 2011 to 2013
$747k
NCI NIH HHS 5R37CA054358-19NCI NIH HHS R37 CA054358NIEHS NIH HHS 1R01ES015445NIEHS NIH HHS R00 ES017051NIEHS NIH HHS R01 ES015445NIEHS NIH HHS R01 ES017646NIEHS NIH HHS R01ES017646
6 · The paper itself

Abstract

backgroundGestational age at birth strongly predicts neonatal, adolescent and adult morbidity and mortality through mostly unknown mechanisms. Identification of specific genes that are undergoing regulatory change prior to birth, such as through changes in DNA methylation, would increase our understanding of developmental changes occurring during the third trimester and consequences of pre-term birth (PTB).

methodsWe performed a genome-wide analysis of DNA methylation (using microarrays, specifically CHARM 2.0) in 141 newborns collected in Baltimore, MD, using novel statistical methodology to identify genomic regions associated with gestational age at birth. Bisulphite pyrosequencing was used to validate significant differentially methylated regions (DMRs), and real-time PCR was performed to assess functional significance of differential methylation in a subset of newborns.

resultsWe identified three DMRs at genome-wide significance levels adjacent to the NFIX, RAPGEF2 and MSRB3 genes. All three regions were validated by pyrosequencing, and RAGPEF2 also showed an inverse correlation between DNA methylation levels and gene expression levels. Although the three DMRs appear very dynamic with gestational age in our newborn sample, adult DNA methylation levels at these regions are stable and of equal or greater magnitude than the oldest neonate, directionally consistent with the gestational age results.

conclusionsWe have identified three differentially methylated regions associated with gestational age at birth. All three nearby genes play important roles in the development of several organs, including skeletal muscle, brain and haematopoietic system. Therefore, they may provide initial insight into the basis of PTB's negative health outcomes. The genome-wide custom DNA methylation array technology and novel statistical methods employed in this study could constitute a model for epidemiologic studies of epigenetic variation.

Indexed as

Gestational AgeAdolescentAdultAgedAged, 80 and overDNA MethylationEpigenesis, GeneticFemaleGenome-Wide Association StudyGuanine Nucleotide Exchange FactorsHumansInfant, NewbornMaleMethionine Sulfoxide ReductasesMiddle AgedNerve Tissue ProteinsGuanine Nucleotide Exchange FactorsMethionine Sulfoxide ReductasesMSRB3 protein, humanNerve Tissue ProteinsNFI Transcription FactorsRAPGEF2 protein, human

Identifiers

PMID22422452
PMCPMC3304532
OpenAlexW2169391326

What OpenQuestion holds

Textmetadata
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.